14-23416678-G-A

Variant names:

• chr14-23416678-G-A
• rs3729829
• NM_000257.4:c.4644+190C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000257.4(MYH7):​c.4644+190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,032 control chromosomes in the GnomAD database, including 15,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (15582 hom., cov: 32)
• Consequence: MYH7 NM_000257.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-23416678-G-A is Benign according to our data. Variant chr14-23416678-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7	NM_000257.4	MANE Select	c.4644+190C>T		intron	N/A	NP_000248.2
	MYH7	NM_001407004.1		c.4644+190C>T		intron	N/A	NP_001393933.1
	MHRT	NR_126491.1		n.559-238G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7	ENST00000355349.4	TSL:1 MANE Select	c.4644+190C>T		intron	N/A	ENSP00000347507.3
	MYH7	ENST00000713768.1		c.4644+190C>T		intron	N/A	ENSP00000519070.1
	MYH7	ENST00000713769.1		c.4644+190C>T		intron	N/A	ENSP00000519071.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63814 AN: 151914 Hom.: 15549 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.0771

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63884 AN: 152032 Hom.: 15582 Cov.: 32 AF XY: 0.407 AC XY: 30271 AN XY: 74340

African (AFR) AF: 0.676 AC: 27998 AN: 41430

American (AMR) AF: 0.290 AC: 4430 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1330 AN: 3468

East Asian (EAS) AF: 0.0773 AC: 400 AN: 5174

South Asian (SAS) AF: 0.215 AC: 1038 AN: 4822

European-Finnish (FIN) AF: 0.262 AC: 2774 AN: 10596

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24578 AN: 67942

Other (OTH) AF: 0.412 AC: 871 AN: 2112

Alfa AF: 0.388 Hom.: 2041

Bravo AF: 0.432

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.38
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs3729829; hg19: chr14-23885887;