rs3729828

chr14-23416788-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000257.4(MYH7):c.4644+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,606,016 control chromosomes in the GnomAD database, including 110,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (15633 hom., cov: 32)
  • Exomes 𝑓: 0.35 (94436 hom.)
• Consequence: MYH7 NM_000257.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0780

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-23416788-G-A is Benign according to our data. Variant chr14-23416788-G-A is described in ClinVar as [Benign]. Clinvar id is 1225999.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23416788-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH7	NM_000257.4	c.4644+80C>T		intron_variant		ENST00000355349.4
MHRT	NR_126491.1	n.559-128G>A		intron_variant, non_coding_transcript_variant
MYH7	NM_001407004.1	c.4644+80C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7	ENST00000355349.4	c.4644+80C>T		intron_variant		1	NM_000257.4	P1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63899 AN: 151932 Hom.: 15600 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.288

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: 0.363

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.349 AC: 507051 AN: 1453966 Hom.: 94436 AF XY: 0.345 AC XY: 249290 AN XY: 723422

Gnomad4 AFR exome AF: 0.686

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.0525

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.421 AC: 63969 AN: 152050 Hom.: 15633 Cov.: 32 AF XY: 0.408 AC XY: 30308 AN XY: 74332

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.411

Alfa AF: 0.409 Hom.: 1817

Bravo AF: 0.432

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.1
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs3729828; hg19: chr14-23885997;