rs11237123

Variant names:

• chr11-77211901-G-A
• rs11237123
• NM_000260.4:c.6318G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000260.4(MYO7A):​c.6318G>A​(p.Lys2106Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,528 control chromosomes in the GnomAD database, including 32,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5062 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27832 hom.)
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 1.83
• Publications: 17 publications found

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, PanelApp Australia
• Usher syndrome type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant nonsyndromic hearing loss 11

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 11-77211901-G-A is Benign according to our data. Variant chr11-77211901-G-A is described in ClinVar as [Benign]. Clinvar id is 43324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.6318G>A	p.Lys2106Lys	synonymous_variant	Exon 46 of 49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.6318G>A	p.Lys2106Lys	synonymous_variant	Exon 46 of 49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.6204G>A	p.Lys2068Lys	synonymous_variant	Exon 46 of 49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.6171G>A	p.Lys2057Lys	synonymous_variant	Exon 47 of 50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.3744G>A	p.Lys1248Lys	synonymous_variant	Exon 26 of 29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.*890G>A		non_coding_transcript_exon_variant	Exon 29 of 32			ENSP00000499323.1
MYO7A	ENST00000670577.1	n.*890G>A		3_prime_UTR_variant	Exon 29 of 32			ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36306 AN: 152050 Hom.: 5033 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.230

GnomAD2 exomes AF: 0.177 AC: 44183 AN: 249168 AF XY: 0.176

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.0981

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.0695

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.188 AC: 274288 AN: 1461360 Hom.: 27832 Cov.: 33 AF XY: 0.185 AC XY: 134769 AN XY: 726982

African (AFR) AF: 0.382 AC: 12799 AN: 33470

American (AMR) AF: 0.103 AC: 4588 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3714 AN: 26134

East Asian (EAS) AF: 0.0459 AC: 1821 AN: 39700

South Asian (SAS) AF: 0.0893 AC: 7704 AN: 86244

European-Finnish (FIN) AF: 0.266 AC: 14203 AN: 53390

Middle Eastern (MID) AF: 0.235 AC: 1356 AN: 5768

European-Non Finnish (NFE) AF: 0.195 AC: 216917 AN: 1111572

Other (OTH) AF: 0.185 AC: 11186 AN: 60362

GnomAD4 genome AF: 0.239 AC: 36389 AN: 152168 Hom.: 5062 Cov.: 32 AF XY: 0.240 AC XY: 17853 AN XY: 74382

African (AFR) AF: 0.370 AC: 15366 AN: 41506

American (AMR) AF: 0.149 AC: 2278 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 484 AN: 3470

East Asian (EAS) AF: 0.0672 AC: 348 AN: 5178

South Asian (SAS) AF: 0.0852 AC: 411 AN: 4824

European-Finnish (FIN) AF: 0.293 AC: 3107 AN: 10588

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13701 AN: 67982

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.212 Hom.: 8144

Bravo AF: 0.234

Asia WGS AF: 0.104 AC: 361 AN: 3478

EpiCase AF: 0.209

EpiControl AF: 0.204

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

Mar 08, 2007

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 22, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 11 Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 2 Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1 Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1B Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	9.4
DANN	Benign	0.81
PhyloP100		1.8
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11237123; hg19: chr11-76922946; COSMIC: COSV60018959; COSMIC: COSV60018959;