rs2276291

Variant names:

• chr11-77207277-T-C
• rs2276291
• NM_000260.4:c.5743-12T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000260.4(MYO7A):​c.5743-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,592,366 control chromosomes in the GnomAD database, including 273,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30386 hom., cov: 31)
  • Exomes 𝑓: 0.58 (242842 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Scores: Splicing: ADA: 0.0001877
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.401

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-77207277-T-C is Benign according to our data. Variant chr11-77207277-T-C is described in ClinVar as [Benign]. Clinvar id is 43297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207277-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.5743-12T>C		intron_variant	Intron 41 of 48	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.5743-12T>C		intron_variant	Intron 41 of 48	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.5629-12T>C		intron_variant	Intron 41 of 48	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.5596-12T>C		intron_variant	Intron 42 of 49	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.3169-12T>C		intron_variant	Intron 21 of 28	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.*341-12T>C		intron_variant	Intron 24 of 31			ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95216 AN: 151836 Hom.: 30330 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.634

GnomAD3 exomes AF: 0.589 AC: 132727 AN: 225270 Hom.: 39793 AF XY: 0.577 AC XY: 70433 AN XY: 122052

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.692

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.508

Gnomad SAS exome AF: 0.437

Gnomad FIN exome AF: 0.656

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.579

GnomAD4 exome AF: 0.577 AC: 831602 AN: 1440412 Hom.: 242842 Cov.: 30 AF XY: 0.573 AC XY: 409855 AN XY: 715568

Gnomad4 AFR exome AF: 0.737

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.483

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.656

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.627 AC: 95342 AN: 151954 Hom.: 30386 Cov.: 31 AF XY: 0.628 AC XY: 46614 AN XY: 74268

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.632

Alfa AF: 0.597 Hom.: 7018

Bravo AF: 0.634

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

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

- -

not specified Benign:2

Jun 23, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 2 Benign:2

Jan 12, 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 dominant nonsyndromic hearing loss 11 Benign:2

Jan 12, 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 12, 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.51
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2276291; hg19: chr11-76918322;