rs883223

Variant names:

• chr11-77213829-G-A
• rs883223
• NM_000260.4:c.6439-31G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77213829-G-A
• chr11-77213829-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.6439-31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,613,084 control chromosomes in the GnomAD database, including 101,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9461 hom., cov: 34)
  • Exomes 𝑓: 0.35 (92434 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0460
• Publications: 14 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=-0.81).
• BP6: Variant 11-77213829-G-A is Benign according to our data. Variant chr11-77213829-G-A is described in ClinVar as Benign. ClinVar VariationId is 255666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.6439-31G>A		intron_variant	Intron 47 of 48	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.6439-31G>A		intron_variant	Intron 47 of 48	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.6319-31G>A		intron_variant	Intron 47 of 48	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.6292-31G>A		intron_variant	Intron 48 of 49	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.3865-31G>A		intron_variant	Intron 27 of 28	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.*1011-31G>A		intron_variant	Intron 30 of 31			ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52823 AN: 152052 Hom.: 9451 Cov.: 34

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.383 AC: 95239 AN: 248736 AF XY: 0.374

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.486

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.361

GnomAD4 exome AF: 0.352 AC: 513534 AN: 1460916 Hom.: 92434 Cov.: 38 AF XY: 0.351 AC XY: 255085 AN XY: 726736

African (AFR) AF: 0.308 AC: 10322 AN: 33462

American (AMR) AF: 0.561 AC: 25073 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 9161 AN: 26126

East Asian (EAS) AF: 0.502 AC: 19926 AN: 39696

South Asian (SAS) AF: 0.373 AC: 32200 AN: 86236

European-Finnish (FIN) AF: 0.337 AC: 17903 AN: 53184

Middle Eastern (MID) AF: 0.344 AC: 1987 AN: 5768

European-Non Finnish (NFE) AF: 0.338 AC: 375617 AN: 1111388

Other (OTH) AF: 0.354 AC: 21345 AN: 60346

GnomAD4 genome AF: 0.347 AC: 52861 AN: 152168 Hom.: 9461 Cov.: 34 AF XY: 0.348 AC XY: 25856 AN XY: 74384

African (AFR) AF: 0.308 AC: 12806 AN: 41536

American (AMR) AF: 0.467 AC: 7137 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1235 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2415 AN: 5152

South Asian (SAS) AF: 0.364 AC: 1755 AN: 4824

European-Finnish (FIN) AF: 0.321 AC: 3402 AN: 10596

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22839 AN: 67980

Other (OTH) AF: 0.345 AC: 730 AN: 2114

Alfa AF: 0.347 Hom.: 11356

Bravo AF: 0.359

Asia WGS AF: 0.388 AC: 1349 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 24, 2018

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: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	-0.81
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		-0.046
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: rs883223; hg19: chr11-76924874; COSMIC: COSV60018097; COSMIC: COSV60018097;