rs883224

Positions:

• chr11-77213995-G-A

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.6558+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,328 control chromosomes in the GnomAD database, including 48,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3567 hom., cov: 34)
  • Exomes 𝑓: 0.24 (44724 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.55

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-77213995-G-A is Benign according to our data. Variant chr11-77213995-G-A is described in ClinVar as [Benign]. Clinvar id is 43332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77213995-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.6558+16G>A		intron_variant		ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.6558+16G>A		intron_variant		1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.6438+16G>A		intron_variant		1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.6411+16G>A		intron_variant		1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.3984+16G>A		intron_variant		1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.*1130+16G>A		intron_variant				ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28571 AN: 152174 Hom.: 3567 Cov.: 34

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.207

GnomAD3 exomes AF: 0.201 AC: 49963 AN: 248448 Hom.: 6296 AF XY: 0.206 AC XY: 27767 AN XY: 134764

Gnomad AFR exome AF: 0.0392

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.0693

Gnomad SAS exome AF: 0.0904

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.237 AC: 346002 AN: 1461036 Hom.: 44724 Cov.: 52 AF XY: 0.235 AC XY: 170758 AN XY: 726766

Gnomad4 AFR exome AF: 0.0386

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.0932

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.188 AC: 28566 AN: 152292 Hom.: 3567 Cov.: 34 AF XY: 0.190 AC XY: 14136 AN XY: 74442

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0699

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.205

Alfa AF: 0.229 Hom.: 828

Bravo AF: 0.166

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 23, 2009	- -
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	-0.78
CADD	Benign	0.53
DANN	Benign	0.82

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: rs883224; hg19: chr11-76925040;