Variant 17-10496580-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005963.4(MYH1):c.4657-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,346 control chromosomes in the GnomAD database, including 163,693 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 14636 hom., cov: 31)

Exomes 𝑓: 0.44 ( 149057 hom. )

Consequence

MYH1
NM_005963.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0650

Variant links:

Genes affected

MYH1 (HGNC:7567): (myosin heavy chain 1) Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. Myosin heavy chains are encoded by a multigene family. In mammals at least 10 different myosin heavy chain (MYH) isoforms have been described from striated, smooth, and nonmuscle cells. These isoforms show expression that is spatially and temporally regulated during development. [provided by RefSeq, Jul 2008]

MYH1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MYH1	NM_005963.4 linkuse as main transcript	c.4657-31T>C	intron_variant	ENST00000226207.6	NP_005954.3
MYHAS	NR_125367.1 linkuse as main transcript	n.168-70957A>G	intron_variant, non_coding_transcript_variant
MYH1	XM_017024675.2 linkuse as main transcript	c.4657-31T>C	intron_variant		XP_016880164.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
MYH1	ENST00000226207.6 linkuse as main transcript	c.4657-31T>C	intron_variant	5	NM_005963.4	ENSP00000226207	P1
	ENST00000399342.6 linkuse as main transcript	n.207-36744A>G	intron_variant, non_coding_transcript_variant	3
	ENST00000581304.1 linkuse as main transcript	n.144-36744A>G	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64578

AN:

151784

Hom.:

14628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.500

AC:

125201

AN:

250176

Hom.:

33913

AF XY:

0.500

AC XY:

67734

AN XY:

135498

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.607

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.874

Gnomad SAS exome

AF:

0.622

Gnomad FIN exome

AF:

0.478

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.457

GnomAD4 exome

AF:

0.441

AC:

644394

AN:

1461444

Hom.:

149057

Cov.:

AF XY:

0.445

AC XY:

323792

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.590

Gnomad4 ASJ exome

AF:

0.461

Gnomad4 EAS exome

AF:

0.843

Gnomad4 SAS exome

AF:

0.620

Gnomad4 FIN exome

AF:

0.467

Gnomad4 NFE exome

AF:

0.408

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.425

AC:

64625

AN:

151902

Hom.:

14636

Cov.:

AF XY:

0.439

AC XY:

32554

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.856

Gnomad4 SAS

AF:

0.638

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.413

Gnomad4 OTH

AF:

0.394

Alfa

AF:

0.415

Hom.:

3958

Bravo

AF:

0.419

Asia WGS

AF:

0.689

AC:

2395

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.5

DANN

Benign

0.69

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over