NM_001613.4:c.455-17G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001613.4(ACTA2):c.455-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00842 in 1,613,720 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 43 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 354 hom. )

Consequence

ACTA2
NM_001613.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.325

Publications

4 publications found

Variant links:

Genes affected

ACTA2 (HGNC:130): (actin alpha 2, smooth muscle) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a smooth muscle actin that is involved in vascular contractility and blood pressure homeostasis. Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, and Moyamoya disease, as well as multisystemic smooth muscle dysfunction syndrome. [provided by RefSeq, Sep 2017]

ACTA2 links:

STAMBPL1 (HGNC:24105): (STAM binding protein like 1) Predicted to enable Lys63-specific deubiquitinase activity and thiol-dependent deubiquitinase. Predicted to be involved in protein K63-linked deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

STAMBPL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-88941407-C-T is Benign according to our data. Variant chr10-88941407-C-T is described in ClinVar as Benign. ClinVar VariationId is 35644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001613.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACTA2	NM_001613.4	MANE Select	c.455-17G>A	intron	N/A	NP_001604.1
ACTA2	NM_001141945.3		c.455-17G>A	intron	N/A	NP_001135417.1
ACTA2	NM_001320855.2		c.455-17G>A	intron	N/A	NP_001307784.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACTA2	ENST00000224784.10	TSL:1 MANE Select	c.455-17G>A	intron	N/A	ENSP00000224784.6
STAMBPL1	ENST00000371927.7	TSL:2	c.1254+18971C>T	intron	N/A	ENSP00000360995.3
ACTA2	ENST00000713598.1		c.497-17G>A	intron	N/A	ENSP00000518894.1

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1271

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0214

Gnomad FIN

AF:

0.000568

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00503

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0146

AC:

3656

AN:

250896

AF XY:

0.0145

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.00408

Gnomad EAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00500

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00842

AC:

12305

AN:

1461606

Hom.:

354

Cov.:

AF XY:

0.00873

AC XY:

6348

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33470

American (AMR)

AF:

0.00271

AC:

121

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00390

AC:

102

AN:

26128

East Asian (EAS)

AF:

0.118

AC:

4676

AN:

39636

South Asian (SAS)

AF:

0.0151

AC:

1302

AN:

86254

European-Finnish (FIN)

AF:

0.000543

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00919

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00473

AC:

5258

AN:

1111844

Other (OTH)

AF:

0.0119

AC:

719

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

647

1293

1940

2586

3233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00839

AC:

1276

AN:

152114

Hom.:

Cov.:

AF XY:

0.00923

AC XY:

686

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41490

American (AMR)

AF:

0.00419

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.121

AC:

627

AN:

5164

South Asian (SAS)

AF:

0.0216

AC:

104

AN:

4810

European-Finnish (FIN)

AF:

0.000568

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00503

AC:

342

AN:

68008

Other (OTH)

AF:

0.0123

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

132

198

264

330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00851

Hom.:

Bravo

AF:

0.00941

Asia WGS

AF:

0.0750

AC:

260

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Mar 21, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Familial aortopathy

Benign:1

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Aortic aneurysm, familial thoracic 6

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.4

(source)

DANN

Benign

0.60

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over