11-77198633-C-G

Variant names:

• chr11-77198633-C-G
• rs72933642
• NM_000260.4:c.4568+12C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000260.4(MYO7A):​c.4568+12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 1,613,342 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (145 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.239

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 11-77198633-C-G is Benign according to our data. Variant chr11-77198633-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 43246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77198633-C-G is described in Lovd as [Benign]. Variant chr11-77198633-C-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00915 (1393/152308) while in subpopulation EAS AF= 0.0133 (69/5182). AF 95% confidence interval is 0.0108. There are 47 homozygotes in gnomad4. There are 939 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.4568+12C>G		intron_variant	Intron 34 of 48	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.4568+12C>G		intron_variant	Intron 34 of 48	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.4568+12C>G		intron_variant	Intron 34 of 48	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.4535+12C>G		intron_variant	Intron 35 of 49	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.2111+12C>G		intron_variant	Intron 14 of 28	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.2408+12C>G		intron_variant	Intron 17 of 31			ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1394 AN: 152192 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00489

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.0107 AC: 2649 AN: 247750 Hom.: 59 AF XY: 0.0106 AC XY: 1431 AN XY: 134574

Gnomad AFR exome AF: 0.000652

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00140

Gnomad EAS exome AF: 0.0136

Gnomad SAS exome AF: 0.00233

Gnomad FIN exome AF: 0.0794

Gnomad NFE exome AF: 0.00476

Gnomad OTH exome AF: 0.00847

GnomAD4 exome AF: 0.00644 AC: 9403 AN: 1461034 Hom.: 145 Cov.: 31 AF XY: 0.00624 AC XY: 4532 AN XY: 726754

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.0100

Gnomad4 SAS exome AF: 0.00280

Gnomad4 FIN exome AF: 0.0704

Gnomad4 NFE exome AF: 0.00413

Gnomad4 OTH exome AF: 0.00539

GnomAD4 genome AF: 0.00915 AC: 1393 AN: 152308 Hom.: 47 Cov.: 33 AF XY: 0.0126 AC XY: 939 AN XY: 74468

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.00489

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00371 Hom.: 1

Bravo AF: 0.00307

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Oct 05, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.4568+12C>G in intron 34 of MYO7A: This variant is not expected to have clinica l significance because it is not located within the conserved splice consensus s equence. It has been identified in 8.6% (546/6314) of Finnish European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs72933642). -

Autosomal dominant nonsyndromic hearing loss 11 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Autosomal recessive nonsyndromic hearing loss 2 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Usher syndrome type 1 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.66

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: rs72933642; hg19: chr11-76909678;