Variant rs59228224 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001100.4(ACTA1):c.809-35del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,608,438 control chromosomes in the GnomAD database, including 27,349 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3438 hom., cov: 27)

Exomes 𝑓: 0.18 ( 23911 hom. )

Consequence

ACTA1
NM_001100.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

ACTA1 (HGNC:129): (actin alpha 1, skeletal muscle) The product encoded by this gene belongs to the actin family of proteins, which are highly conserved proteins that play a role in cell motility, structure and integrity. Alpha, beta and gamma actin isoforms have been identified, with alpha actins being a major constituent of the contractile apparatus, while beta and gamma actins are involved in the regulation of cell motility. This actin is an alpha actin that is found in skeletal muscle. Mutations in this gene cause a variety of myopathies, including nemaline myopathy, congenital myopathy with excess of thin myofilaments, congenital myopathy with cores, and congenital myopathy with fiber-type disproportion, diseases that lead to muscle fiber defects with manifestations such as hypotonia. [provided by RefSeq, Sep 2019]

ACTA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-229431936-TC-T is Benign according to our data. Variant chr1-229431936-TC-T is described in ClinVar as [Benign]. Clinvar id is 93554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-229431936-TC-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTA1	NM_001100.4 linkuse as main transcript	c.809-35del		intron_variant		ENST00000366684.7	NP_001091.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ACTA1	ENST00000366684.7 linkuse as main transcript	c.809-35del	intron_variant	1	NM_001100.4	ENSP00000355645	P1
ACTA1	ENST00000366683.4 linkuse as main transcript	c.809-35del	intron_variant	5		ENSP00000355644
ACTA1	ENST00000684723.1 linkuse as main transcript	c.674-35del	intron_variant			ENSP00000508084

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31071

AN:

151054

Hom.:

3427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.146

AC:

31739

AN:

217818

Hom.:

3779

AF XY:

0.143

AC XY:

17036

AN XY:

119100

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.0920

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.178

AC:

260120

AN:

1457272

Hom.:

23911

Cov.:

AF XY:

0.178

AC XY:

128917

AN XY:

724270

show subpopulations

Gnomad4 AFR exome

AF:

0.279

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.174

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.206

AC:

31110

AN:

151166

Hom.:

3438

Cov.:

AF XY:

0.204

AC XY:

15036

AN XY:

73840

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.118

Hom.:

267

Asia WGS

AF:

0.162

AC:

561

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 13, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over