rs883224

Variant names:

• chr11-77213995-G-A
• rs883224
• NM_000260.4:c.6558+16G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77213995-G-A
• chr11-77213995-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000260.4(MYO7A):​c.6558+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,328 control chromosomes in the GnomAD database, including 48,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3567 hom., cov: 34)
  • Exomes 𝑓: 0.24 (44724 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.55
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-77213995-G-A is Benign according to our data. Variant chr11-77213995-G-A is described in ClinVar as Benign. ClinVar VariationId is 43332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	NM_000260.4	MANE Select	c.6558+16G>A		intron	N/A	NP_000251.3
	MYO7A	NM_001127180.2		c.6438+16G>A		intron	N/A	NP_001120652.1
	MYO7A	NM_001369365.1		c.6411+16G>A		intron	N/A	NP_001356294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.6558+16G>A		intron	N/A	ENSP00000386331.3
	MYO7A	ENST00000458637.6	TSL:1	c.6438+16G>A		intron	N/A	ENSP00000392185.2
	MYO7A	ENST00000409619.6	TSL:1	c.6411+16G>A		intron	N/A	ENSP00000386635.2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28571 AN: 152174 Hom.: 3567 Cov.: 34

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.201 AC: 49963 AN: 248448 AF XY: 0.206

Gnomad AFR exome AF: 0.0392

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.0693

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.237 AC: 346002 AN: 1461036 Hom.: 44724 Cov.: 52 AF XY: 0.235 AC XY: 170758 AN XY: 726766

African (AFR) AF: 0.0386 AC: 1292 AN: 33468

American (AMR) AF: 0.113 AC: 5071 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6242 AN: 26132

East Asian (EAS) AF: 0.0455 AC: 1804 AN: 39684

South Asian (SAS) AF: 0.0932 AC: 8034 AN: 86174

European-Finnish (FIN) AF: 0.344 AC: 18321 AN: 53286

Middle Eastern (MID) AF: 0.245 AC: 1415 AN: 5764

European-Non Finnish (NFE) AF: 0.262 AC: 291059 AN: 1111470

Other (OTH) AF: 0.212 AC: 12764 AN: 60348

GnomAD4 genome AF: 0.188 AC: 28566 AN: 152292 Hom.: 3567 Cov.: 34 AF XY: 0.190 AC XY: 14136 AN XY: 74442

African (AFR) AF: 0.0444 AC: 1848 AN: 41578

American (AMR) AF: 0.155 AC: 2372 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3472

East Asian (EAS) AF: 0.0699 AC: 363 AN: 5190

South Asian (SAS) AF: 0.0876 AC: 423 AN: 4828

European-Finnish (FIN) AF: 0.372 AC: 3941 AN: 10586

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18166 AN: 68010

Other (OTH) AF: 0.205 AC: 434 AN: 2114

Alfa AF: 0.229 Hom.: 828

Bravo AF: 0.166

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 23, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal recessive nonsyndromic hearing loss 2 Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal dominant nonsyndromic hearing loss 11 Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Usher syndrome type 1 Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.53
DANN	Benign	0.82
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs883224; hg19: chr11-76925040; COSMIC: COSV107330819; COSMIC: COSV107330819;