11-77190882-C-T

Variant names:

• chr11-77190882-C-T
• rs2276285
• NM_000260.4:c.3924+12C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000409709.9(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 ENST00000409709.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.0760
• Publications: 15 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=-0.83).
• BP6: Variant 11-77190882-C-T is Benign according to our data. Variant chr11-77190882-C-T is described in ClinVar as Benign. ClinVar VariationId is 43226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409709.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	NM_000260.4	MANE Select	c.3924+12C>T		intron	N/A	NP_000251.3
	MYO7A	NM_001127180.2		c.3924+12C>T		intron	N/A	NP_001120652.1
	MYO7A	NM_001369365.1		c.3891+12C>T		intron	N/A	NP_001356294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.3924+12C>T		intron	N/A	ENSP00000386331.3
	MYO7A	ENST00000458637.6	TSL:1	c.3924+12C>T		intron	N/A	ENSP00000392185.2
	MYO7A	ENST00000409619.6	TSL:1	c.3891+12C>T		intron	N/A	ENSP00000386635.2

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

GnomAD2 exomes AF: 0.518 AC: 87106 AN: 168156 AF XY: 0.506

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 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

African (AFR) AF: 0.430 AC: 13340 AN: 31000

American (AMR) AF: 0.625 AC: 21651 AN: 34656

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 9149 AN: 24224

East Asian (EAS) AF: 0.477 AC: 17074 AN: 35760

South Asian (SAS) AF: 0.368 AC: 28911 AN: 78530

European-Finnish (FIN) AF: 0.617 AC: 30290 AN: 49106

Middle Eastern (MID) AF: 0.388 AC: 2150 AN: 5540

European-Non Finnish (NFE) AF: 0.538 AC: 573875 AN: 1066922

Other (OTH) AF: 0.494 AC: 28164 AN: 57018

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

African (AFR) AF: 0.440 AC: 18117 AN: 41182

American (AMR) AF: 0.588 AC: 8973 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1314 AN: 3446

East Asian (EAS) AF: 0.468 AC: 2404 AN: 5140

South Asian (SAS) AF: 0.344 AC: 1654 AN: 4808

European-Finnish (FIN) AF: 0.618 AC: 6531 AN: 10568

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36013 AN: 67898

Other (OTH) AF: 0.504 AC: 1061 AN: 2104

Alfa AF: 0.518 Hom.: 55526

Bravo AF: 0.504

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Autosomal dominant nonsyndromic hearing loss 11 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 2 (2)
-	-	2	Usher syndrome type 1 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.5
DANN	Benign	0.68
PhyloP100		0.076
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2276285; hg19: chr11-76901927; COSMIC: COSV68686532;