rs111033477

Variant names:

• chr11-77203106-C-A
• rs111033477
• NM_000260.4:c.5215C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77203106-C-A
• chr11-77203106-C-T
• chr11-77203106-C-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BS1 BS2

The NM_000260.4(MYO7A):​c.5215C>A​(p.Arg1739Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0013 in 1,549,206 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (13 hom.)
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 5.64
• Publications: 4 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 Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss 11

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).
• BP6: Variant 11-77203106-C-A is Benign according to our data. Variant chr11-77203106-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00688 (1048/152312) while in subpopulation AFR AF = 0.0239 (995/41572). AF 95% confidence interval is 0.0227. There are 6 homozygotes in GnomAd4. There are 483 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	NM_000260.4	MANE Select	c.5215C>A	p.Arg1739Arg	synonymous	Exon 38 of 49	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.5101C>A	p.Arg1701Arg	synonymous	Exon 38 of 49	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.5068C>A	p.Arg1690Arg	synonymous	Exon 39 of 50	NP_001356294.1	Q13402-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.5215C>A	p.Arg1739Arg	synonymous	Exon 38 of 49	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.5101C>A	p.Arg1701Arg	synonymous	Exon 38 of 49	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.5068C>A	p.Arg1690Arg	synonymous	Exon 39 of 50	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1045 AN: 152194 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00135 AC: 207 AN: 153198 AF XY: 0.00104

Gnomad AFR exome AF: 0.0236

Gnomad AMR exome AF: 0.000648

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000170

Gnomad OTH exome AF: 0.000925

GnomAD4 exome AF: 0.000692 AC: 966 AN: 1396894 Hom.: 13 Cov.: 31 AF XY: 0.000591 AC XY: 407 AN XY: 689064

African (AFR) AF: 0.0263 AC: 829 AN: 31546

American (AMR) AF: 0.00104 AC: 37 AN: 35738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35764

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48502

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4092

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1079084

Other (OTH) AF: 0.00147 AC: 85 AN: 57836

GnomAD4 genome AF: 0.00688 AC: 1048 AN: 152312 Hom.: 6 Cov.: 33 AF XY: 0.00649 AC XY: 483 AN XY: 74470

African (AFR) AF: 0.0239 AC: 995 AN: 41572

American (AMR) AF: 0.00229 AC: 35 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00246 Hom.: 5

Bravo AF: 0.00816

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 11 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 2 (1)
-	-	1	Usher syndrome type 1 (1)
-	-	1	Usher syndrome type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		5.6
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs111033477; hg19: chr11-76914151;