rs2276289

Positions:

• chr11-77213085-A-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.6438+50A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,435,954 control chromosomes in the GnomAD database, including 639,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (59128 hom., cov: 30)
  • Exomes 𝑓: 0.95 (580165 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.908

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=-0.95).
• BP6: Variant 11-77213085-A-T is Benign according to our data. Variant chr11-77213085-A-T is described in ClinVar as [Benign]. Clinvar id is 255665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77213085-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.6438+50A>T		intron_variant		ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.6438+50A>T		intron_variant		1	NM_000260.4	ENSP00000386331

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132500 AN: 152020 Hom.: 59082 Cov.: 30

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.960

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.885

GnomAD3 exomes AF: 0.914 AC: 143017 AN: 156556 Hom.: 65896 AF XY: 0.918 AC XY: 75804 AN XY: 82594

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.881

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 0.774

Gnomad SAS exome AF: 0.898

Gnomad FIN exome AF: 0.958

Gnomad NFE exome AF: 0.970

Gnomad OTH exome AF: 0.932

GnomAD4 exome AF: 0.949 AC: 1217908 AN: 1283816 Hom.: 580165 Cov.: 18 AF XY: 0.948 AC XY: 606290 AN XY: 639468

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.881

Gnomad4 ASJ exome AF: 0.977

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.896

Gnomad4 FIN exome AF: 0.962

Gnomad4 NFE exome AF: 0.970

Gnomad4 OTH exome AF: 0.928

GnomAD4 genome AF: 0.872 AC: 132602 AN: 152138 Hom.: 59128 Cov.: 30 AF XY: 0.871 AC XY: 64770 AN XY: 74390

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.960

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.884

Alfa AF: 0.928 Hom.: 12134

Bravo AF: 0.858

Asia WGS AF: 0.832 AC: 2894 AN: 3478

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	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	-0.95
CADD	Benign	0.48
DANN	Benign	0.46

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: rs2276289; hg19: chr11-76924130;