rs7140196

Variant names:

• chr14-23416241-G-A
• rs7140196
• NM_000257.4:c.4716C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-23416241-G-A
• chr14-23416241-G-C
• chr14-23416241-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.4716C>T (p.Ile1572=) variant in the MYH7 gene is 4.59% (514/10406) of African chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372). LINK:https://erepo.genome.network/evrepo/ui/classification/CA015251/MONDO:0004994/002

• Frequency:
  • Genomes: 𝑓 0.013 (65 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (57 hom.)
• Consequence: MYH7 NM_000257.4 synonymous
• Clinical Significance: Benign reviewed by expert panel B:22
• Conservation: PhyloP100: -3.04
• Publications: 2 publications found

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]

MHRT (HGNC:51291): (myosin heavy chain associated RNA transcript) This gene encodes a spliced long non-coding RNA that may act as a cardioprotective agent in the heart. Based on a study of a similar gene in mouse, the encoded transcript may regulate chromatin remodeling by acting as a decoy to the BRG1 chromatin repressor complex thus preventing it from binding to its genomic targets. Blocking the actions of BRG1 could be crucial in protecting the heart from pathological hypertrophy. [provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000257.4. 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
	MYH7	NM_000257.4	MANE Select	c.4716C>T	p.Ile1572Ile	synonymous	Exon 34 of 40	NP_000248.2
	MYH7	NM_001407004.1		c.4716C>T	p.Ile1572Ile	synonymous	Exon 33 of 39	NP_001393933.1
	MHRT	NR_126491.1		n.502G>A		non_coding_transcript_exon	Exon 3 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7	ENST00000355349.4	TSL:1 MANE Select	c.4716C>T	p.Ile1572Ile	synonymous	Exon 34 of 40	ENSP00000347507.3
	MYH7	ENST00000858540.1		c.4716C>T	p.Ile1572Ile	synonymous	Exon 34 of 40	ENSP00000528599.1
	MYH7	ENST00000965955.1		c.4716C>T	p.Ile1572Ile	synonymous	Exon 34 of 40	ENSP00000636014.1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2013 AN: 151928 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00357 AC: 898 AN: 251366 AF XY: 0.00238

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00150 AC: 2188 AN: 1461802 Hom.: 57 Cov.: 34 AF XY: 0.00123 AC XY: 891 AN XY: 727182

African (AFR) AF: 0.0524 AC: 1754 AN: 33480

American (AMR) AF: 0.00253 AC: 113 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000612 AC: 16 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5764

European-Non Finnish (NFE) AF: 0.000101 AC: 112 AN: 1111946

Other (OTH) AF: 0.00291 AC: 176 AN: 60394

GnomAD4 genome AF: 0.0133 AC: 2019 AN: 152046 Hom.: 65 Cov.: 32 AF XY: 0.0124 AC XY: 918 AN XY: 74326

African (AFR) AF: 0.0455 AC: 1886 AN: 41450

American (AMR) AF: 0.00570 AC: 87 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67996

Other (OTH) AF: 0.0147 AC: 31 AN: 2110

Alfa AF: 0.00726 Hom.: 6

Bravo AF: 0.0148

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	3	Cardiomyopathy (3)
-	-	3	not provided (3)
-	-	2	Hypertrophic cardiomyopathy (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Dilated Cardiomyopathy, Dominant (1)
-	-	1	Hypertrophic cardiomyopathy 1 (1)
-	-	1	Left ventricular noncompaction cardiomyopathy (1)
-	-	1	MYH7-related skeletal myopathy (1)
-	-	1	Myosin storage myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.36
DANN	Benign	0.88
PhyloP100		-3.0
Mutation Taster		=98/2	polymorphism

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: rs7140196; hg19: chr14-23885450; COSMIC: COSV62518841; COSMIC: COSV62518841;