11-77183190-G-C

Variant names:

• chr11-77183190-G-C
• rs948972
• NM_000260.4:c.3375+33G>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.3375+33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,542,458 control chromosomes in the GnomAD database, including 239,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27406 hom., cov: 33)
  • Exomes 𝑓: 0.55 (212459 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.21
• Publications: 11 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=-0.89).
• BP6: Variant 11-77183190-G-C is Benign according to our data. Variant chr11-77183190-G-C is described in ClinVar as Benign. ClinVar VariationId is 255662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.3375+33G>C		intron_variant	Intron 26 of 48	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.3375+33G>C		intron_variant	Intron 26 of 48	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.3375+33G>C		intron_variant	Intron 26 of 48	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.3342+33G>C		intron_variant	Intron 27 of 49	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.918+33G>C		intron_variant	Intron 6 of 28	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.1215+33G>C		intron_variant	Intron 9 of 31			ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90199 AN: 152054 Hom.: 27360 Cov.: 33

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.573

GnomAD2 exomes AF: 0.545 AC: 82897 AN: 152118 AF XY: 0.528

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.519

GnomAD4 exome AF: 0.549 AC: 763561 AN: 1390286 Hom.: 212459 Cov.: 28 AF XY: 0.543 AC XY: 372430 AN XY: 686256

African (AFR) AF: 0.707 AC: 22221 AN: 31412

American (AMR) AF: 0.655 AC: 23387 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 10088 AN: 25104

East Asian (EAS) AF: 0.468 AC: 16691 AN: 35678

South Asian (SAS) AF: 0.379 AC: 29909 AN: 78992

European-Finnish (FIN) AF: 0.608 AC: 29392 AN: 48344

Middle Eastern (MID) AF: 0.419 AC: 2316 AN: 5530

European-Non Finnish (NFE) AF: 0.559 AC: 599065 AN: 1071826

Other (OTH) AF: 0.528 AC: 30492 AN: 57714

GnomAD4 genome AF: 0.593 AC: 90301 AN: 152172 Hom.: 27406 Cov.: 33 AF XY: 0.593 AC XY: 44104 AN XY: 74402

African (AFR) AF: 0.710 AC: 29462 AN: 41510

American (AMR) AF: 0.632 AC: 9667 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2376 AN: 5170

South Asian (SAS) AF: 0.357 AC: 1720 AN: 4818

European-Finnish (FIN) AF: 0.608 AC: 6446 AN: 10604

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.550 AC: 37428 AN: 67994

Other (OTH) AF: 0.570 AC: 1202 AN: 2108

Alfa AF: 0.456 Hom.: 2182

Bravo AF: 0.606

Asia WGS AF: 0.440 AC: 1529 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.61
PhyloP100		-1.2
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: rs948972; hg19: chr11-76894235;