rs111033503

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000260.4(MYO7A):c.736-15_736-4dupTGCCCACATTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,591,982 control chromosomes in the GnomAD database, including 137 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 79 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 58 hom. )

Consequence

MYO7A
NM_000260.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.25

Publications

1 publications found

Variant links:

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

MYO7A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 11-77157263-G-GTGCCCACATTTT is Benign according to our data. Variant chr11-77157263-G-GTGCCCACATTTT is described in ClinVar as Benign. ClinVar VariationId is 43342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.736-15_736-4dupTGCCCACATTTT		splice_region_variant, intron_variant	Intron 7 of 48	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.736-16_736-15insTGCCCACATTTT	intron_variant	Intron 7 of 48	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.736-16_736-15insTGCCCACATTTT	intron_variant	Intron 7 of 48	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.703-16_703-15insTGCCCACATTTT	intron_variant	Intron 8 of 49	1		ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2674

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00431

AC:

973

AN:

225834

AF XY:

0.00321

show subpopulations

Gnomad AFR exome

AF:

0.0508

Gnomad AMR exome

AF:

0.00335

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000522

Gnomad OTH exome

AF:

0.00334

GnomAD4 exome

AF:

0.00218

AC:

3139

AN:

1439660

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

1345

AN XY:

715366

show subpopulations

African (AFR)

AF:

0.0588

AC:

1919

AN:

32620

American (AMR)

AF:

0.00409

AC:

172

AN:

42094

Ashkenazi Jewish (ASJ)

AF:

0.0145

AC:

375

AN:

25860

East Asian (EAS)

AF:

0.00

AC:

AN:

39094

South Asian (SAS)

AF:

0.000131

AC:

AN:

83810

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52556

Middle Eastern (MID)

AF:

0.00349

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.000277

AC:

304

AN:

1098204

Other (OTH)

AF:

0.00565

AC:

337

AN:

59684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

149

298

447

596

745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0177

AC:

2690

AN:

152322

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1287

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0590

AC:

2454

AN:

41560

American (AMR)

AF:

0.00765

AC:

117

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68032

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

128

256

385

513

641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0120

Hom.:

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 26, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 30, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.736-15_736-4dup in intron 7 of MYO7A: This variant is not expected to have cli nical significance because it has been identified in 6.9% (343/4990) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs111537161). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over