rs2071151

Positions:

• chr11-77159412-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000260.4(MYO7A):​c.1004-35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (992 hom., cov: 31)
  • Exomes 𝑓: 0.089 (8793 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0520

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-77159412-C-G is Benign according to our data. Variant chr11-77159412-C-G is described in ClinVar as [Benign]. Clinvar id is 255659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77159412-C-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.1004-35C>G		intron_variant		ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.1004-35C>G		intron_variant		1	NM_000260.4	ENSP00000386331
MYO7A	ENST00000409619.6	c.971-35C>G		intron_variant		1		ENSP00000386635
MYO7A	ENST00000458637.6	c.1004-35C>G		intron_variant		1		ENSP00000392185	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 14976 AN: 151056 Hom.: 988 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0534

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0992 AC: 23684 AN: 238868 Hom.: 1817 AF XY: 0.0936 AC XY: 12188 AN XY: 130242

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.0861

Gnomad EAS exome AF: 0.284

Gnomad SAS exome AF: 0.0985

Gnomad FIN exome AF: 0.0481

Gnomad NFE exome AF: 0.0546

Gnomad OTH exome AF: 0.0867

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0886 AC: 93178 AN: 1051362 Hom.: 8793 Cov.: 21 AF XY: 0.0866 AC XY: 46742 AN XY: 539900

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.0923

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0468

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.0993

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0992 AC: 14995 AN: 151172 Hom.: 992 Cov.: 31 AF XY: 0.0997 AC XY: 7361 AN XY: 73832

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0467

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0781 Hom.: 111

Bravo AF: 0.110

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.59

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: rs2071151; hg19: chr11-76870458; COSMIC: COSV68684107;