Variant rs144658220 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_001100.4(ACTA1):c.129+31C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00828 in 1,613,690 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 104 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 396 hom. )

Consequence

ACTA1
NM_001100.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.284

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:

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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=-0.86).

BP6

Variant 1-229432956-G-T is Benign according to our data. Variant chr1-229432956-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 257442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-229432956-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0742 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.129+31C>A		intron_variant		ENST00000366684.7	NP_001091.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ACTA1	ENST00000366684.7 linkuse as main transcript	c.129+31C>A	intron_variant	1	NM_001100.4	ENSP00000355645	P1
ACTA1	ENST00000366683.4 linkuse as main transcript	c.129+31C>A	intron_variant	5		ENSP00000355644
ACTA1	ENST00000684723.1 linkuse as main transcript	c.-6-76C>A	intron_variant			ENSP00000508084

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2506

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0770

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00415

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0202

AC:

4968

AN:

245466

Hom.:

266

AF XY:

0.0164

AC XY:

2188

AN XY:

133686

show subpopulations

Gnomad AFR exome

AF:

0.0212

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.00131

Gnomad EAS exome

AF:

0.0000550

Gnomad SAS exome

AF:

0.00612

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00344

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.00742

AC:

10841

AN:

1461392

Hom.:

396

Cov.:

AF XY:

0.00696

AC XY:

5062

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00591

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.00342

Gnomad4 OTH exome

AF:

0.00817

GnomAD4 genome

AF:

0.0165

AC:

2520

AN:

152298

Hom.:

104

Cov.:

AF XY:

0.0173

AC XY:

1288

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.0779

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00891

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00415

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.0232

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 01, 2017	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely 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

-0.86

CADD

Benign

1.3

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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