rs45490796

Positions:

chr14-23428711-TG-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000257.4(MYH7):c.1408-42delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,613,416 control chromosomes in the GnomAD database, including 90 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 57 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MYH7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 14-23428711-TG-T is Benign according to our data. Variant chr14-23428711-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 36635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23428711-TG-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1924/152152) while in subpopulation AFR AF= 0.0442 (1832/41480). AF 95% confidence interval is 0.0425. There are 33 homozygotes in gnomad4. There are 909 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7	NM_000257.4 link	c.1408-42delC		intron_variant		ENST00000355349.4	NP_000248.2	P12883
MYH7	NM_001407004.1 link	c.1408-42delC		intron_variant			NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4 link	c.1408-42delC		intron_variant		1	NM_000257.4	ENSP00000347507.3		P12883

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1919

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00816

GnomAD3 exomes

AF:

0.00315

AC:

786

AN:

249484

Hom.:

AF XY:

0.00222

AC XY:

299

AN XY:

134844

show subpopulations

Gnomad AFR exome

AF:

0.0422

Gnomad AMR exome

AF:

0.00175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000240

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00146

AC:

2134

AN:

1461264

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

935

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.0488

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.0126

AC:

1924

AN:

152152

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

909

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0442

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00807

Alfa

AF:

0.00655

Hom.:

Bravo

AF:

0.0137

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jun 01, 2016	Variant summary: The MYH7 c.1408-42delC variant involves the alteration of a non-conserved deep intronic nucleotide. One in silico tool (Mutation Taster) predicts a benign outcome for this variant. In addition, 5/5 splicing algorithms predict no significant change to normal splicing. This variant was found in 470/119028 control chromosomes (including 6 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.041806 (425/10166). This frequency is about 42 times greater than the estimated maximal expected allele frequency of a pathogenic MYH7 variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, one clinical diagnostic laboratory classified this variant as likely benign. Taken together, this variant is classified as benign. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over