rs2276283

chr11-77174733-G-Achr11-77174733-G-Cchr11-77174733-G-T

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.1936-23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,557,772 control chromosomes in the GnomAD database, including 226,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21056 hom., cov: 33)
  • Exomes 𝑓: 0.54 (205164 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0280

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=-0.8).
• BP6: Variant 11-77174733-G-A is Benign according to our data. Variant chr11-77174733-G-A is described in ClinVar as [Benign]. Clinvar id is 255661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77174733-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4	c.1936-23G>A		intron_variant		ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9	c.1936-23G>A		intron_variant		1	NM_000260.4
MYO7A	ENST00000409619.6	c.1903-23G>A		intron_variant		1
MYO7A	ENST00000458637.6	c.1936-23G>A		intron_variant		1		P1
MYO7A	ENST00000409893.6			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79436 AN: 151934 Hom.: 21049 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.519

GnomAD3 exomes AF: 0.528 AC: 90162 AN: 170746 Hom.: 24555 AF XY: 0.515 AC XY: 47207 AN XY: 91586

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.646

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.478

Gnomad SAS exome AF: 0.378

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.504

GnomAD4 exome AF: 0.537 AC: 755049 AN: 1405720 Hom.: 205164 Cov.: 39 AF XY: 0.532 AC XY: 369113 AN XY: 694134

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.638

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.634

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.523 AC: 79467 AN: 152052 Hom.: 21056 Cov.: 33 AF XY: 0.526 AC XY: 39085 AN XY: 74348

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.517

Alfa AF: 0.508 Hom.: 3600

Bravo AF: 0.522

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.4
Dann	Benign	0.68

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: rs2276283; hg19: chr11-76885779; COSMIC: COSV68684715; COSMIC: COSV68684715;