rs1320702

chr11-77208820-T-Achr11-77208820-T-G

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.6051+17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,517,806 control chromosomes in the GnomAD database, including 242,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24181 hom., cov: 33)
  • Exomes 𝑓: 0.56 (217826 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.927

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=-0.81).
• BP6: Variant 11-77208820-T-A is Benign according to our data. Variant chr11-77208820-T-A is described in ClinVar as [Benign]. Clinvar id is 43315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77208820-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4	c.6051+17T>A		intron_variant		ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9	c.6051+17T>A		intron_variant		1	NM_000260.4

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85319 AN: 152036 Hom.: 24143 Cov.: 33

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.580

GnomAD3 exomes AF: 0.566 AC: 90943 AN: 160660 Hom.: 26312 AF XY: 0.556 AC XY: 47238 AN XY: 84982

Gnomad AFR exome AF: 0.518

Gnomad AMR exome AF: 0.670

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.506

Gnomad SAS exome AF: 0.429

Gnomad FIN exome AF: 0.656

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.562 AC: 767487 AN: 1365652 Hom.: 217826 Cov.: 27 AF XY: 0.558 AC XY: 377451 AN XY: 676020

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.652

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.552

GnomAD4 genome AF: 0.561 AC: 85420 AN: 152154 Hom.: 24181 Cov.: 33 AF XY: 0.563 AC XY: 41898 AN XY: 74388

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.579

Alfa AF: 0.502 Hom.: 2667

Bravo AF: 0.561

Asia WGS AF: 0.445 AC: 1548 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 23, 2009	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Autosomal recessive nonsyndromic hearing loss 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Autosomal dominant nonsyndromic hearing loss 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Usher syndrome type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.10
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs1320702; hg19: chr11-76919865; COSMIC: COSV68686298; COSMIC: COSV68686298;