11-77190882-C-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.3924+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,534,358 control chromosomes in the GnomAD database, including 211,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19657 hom., cov: 32)
  • Exomes 𝑓: 0.52 (192202 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.0760

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=-0.83).
• BP6: Variant 11-77190882-C-T is Benign according to our data. Variant chr11-77190882-C-T is described in ClinVar as [Benign]. Clinvar id is 43226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77190882-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4	c.3924+12C>T		intron_variant		ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9	c.3924+12C>T		intron_variant		1	NM_000260.4

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76584 AN: 151492 Hom.: 19643 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.507

GnomAD3 exomes AF: 0.518 AC: 87106 AN: 168156 Hom.: 23181 AF XY: 0.506 AC XY: 45565 AN XY: 89984

Gnomad AFR exome AF: 0.439

Gnomad AMR exome AF: 0.635

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.483

Gnomad SAS exome AF: 0.366

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.533

Gnomad OTH exome AF: 0.500

GnomAD4 exome AF: 0.524 AC: 724604 AN: 1382756 Hom.: 192202 Cov.: 37 AF XY: 0.519 AC XY: 351809 AN XY: 678500

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.538

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.505 AC: 76627 AN: 151602 Hom.: 19657 Cov.: 32 AF XY: 0.508 AC XY: 37660 AN XY: 74088

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.504

Alfa AF: 0.521 Hom.: 31092

Bravo AF: 0.504

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal dominant nonsyndromic hearing loss 11 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Usher syndrome type 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.5
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2276285; hg19: chr11-76901927; COSMIC: COSV68686532;