chr14-23412977-T-G

Position:

• chr14-23412977-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000257.4(MYH7):​c.5791-106A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,181,558 control chromosomes in the GnomAD database, including 81,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (15798 hom., cov: 32)
  • Exomes 𝑓: 0.34 (65730 hom.)
• Consequence: MYH7 NM_000257.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-23412977-T-G is Benign according to our data. Variant chr14-23412977-T-G is described in ClinVar as [Benign]. Clinvar id is 671943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23412977-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7	NM_000257.4	c.5791-106A>C		intron_variant		ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1	c.5791-106A>C		intron_variant			NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4	c.5791-106A>C		intron_variant		1	NM_000257.4	ENSP00000347507.3

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64264 AN: 151922 Hom.: 15764 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.344 AC: 354105 AN: 1029520 Hom.: 65730 AF XY: 0.340 AC XY: 179768 AN XY: 528762

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.0456

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.423 AC: 64333 AN: 152038 Hom.: 15798 Cov.: 32 AF XY: 0.410 AC XY: 30439 AN XY: 74326

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.0686

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.412

Alfa AF: 0.407 Hom.: 1725

Bravo AF: 0.434

Asia WGS AF: 0.184 AC: 642 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs7149517; hg19: chr14-23882186;