Variant rs45468101 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000257.4(MYH7):c.5284-45G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,614,246 control chromosomes in the GnomAD database, including 409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 43 hom., cov: 32)

Exomes 𝑓: 0.012 ( 366 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.20

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 14-23415315-C-A is Benign according to our data. Variant chr14-23415315-C-A is described in ClinVar as [Benign]. Clinvar id is 188643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23415315-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7	NM_000257.4 linkuse as main transcript	c.5284-45G>T		intron_variant		ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1 linkuse as main transcript	c.5284-45G>T		intron_variant			NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4 linkuse as main transcript	c.5284-45G>T		intron_variant		1	NM_000257.4	ENSP00000347507	P1
	ENST00000557368.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2236

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00984

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.0758

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.00677

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.00894

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0218

AC:

5492

AN:

251484

Hom.:

141

AF XY:

0.0217

AC XY:

2946

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00910

Gnomad AMR exome

AF:

0.0360

Gnomad ASJ exome

AF:

0.0305

Gnomad EAS exome

AF:

0.0759

Gnomad SAS exome

AF:

0.0327

Gnomad FIN exome

AF:

0.00707

Gnomad NFE exome

AF:

0.00948

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0125

AC:

18271

AN:

1461892

Hom.:

366

Cov.:

AF XY:

0.0132

AC XY:

9601

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00995

Gnomad4 AMR exome

AF:

0.0347

Gnomad4 ASJ exome

AF:

0.0335

Gnomad4 EAS exome

AF:

0.0819

Gnomad4 SAS exome

AF:

0.0315

Gnomad4 FIN exome

AF:

0.00659

Gnomad4 NFE exome

AF:

0.00698

Gnomad4 OTH exome

AF:

0.0180

GnomAD4 genome

AF:

0.0148

AC:

2256

AN:

152354

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1177

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00993

Gnomad4 AMR

AF:

0.0241

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.0760

Gnomad4 SAS

AF:

0.0360

Gnomad4 FIN

AF:

0.00677

Gnomad4 NFE

AF:

0.00894

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.00875

Hom.:

Bravo

AF:

0.0170

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.34

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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