dbSNP rs77086884: ACTA2:c.*211G>A (chr10-88935012-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000713597.1(ACTA2):c.*211G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 569,254 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 8 hom. )

Consequence

ACTA2
ENST00000713597.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.91

Publications

0 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:

ACTA2-AS1 (HGNC:45169): (ACTA2 antisense RNA 1)

ACTA2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-88935012-C-T is Benign according to our data. Variant chr10-88935012-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1198277.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2081/152054) while in subpopulation AFR AF = 0.0474 (1967/41464). AF 95% confidence interval is 0.0457. There are 34 homozygotes in GnomAd4. There are 983 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2081 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000713597.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTA2-AS1	NR_125373.1		n.637C>T	non_coding_transcript_exon	Exon 3 of 5
ACTA2	NM_001613.4	MANE Select	c.*211G>A	downstream_gene	N/A	NP_001604.1	P62736
ACTA2	NM_001141945.3		c.*211G>A	downstream_gene	N/A	NP_001135417.1	D2JYH4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTA2	ENST00000713597.1		c.*211G>A	3_prime_UTR	Exon 10 of 10	ENSP00000518893.1	P62736
STAMBPL1	ENST00000371927.7	TSL:2	c.1254+12576C>T	intron	N/A	ENSP00000360995.3	Q96FJ0-2
ACTA2-AS1	ENST00000437930.4	TSL:2	n.678C>T	non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2076

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0474

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0100

GnomAD4 exome

AF:

0.00162

AC:

675

AN:

417200

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

298

AN XY:

220130

show subpopulations

African (AFR)

AF:

0.0474

AC:

537

AN:

11318

American (AMR)

AF:

0.00246

AC:

AN:

17042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11080

East Asian (EAS)

AF:

0.00

AC:

AN:

22988

South Asian (SAS)

AF:

0.0000646

AC:

AN:

46424

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22392

Middle Eastern (MID)

AF:

0.000610

AC:

AN:

1640

European-Non Finnish (NFE)

AF:

0.0000802

AC:

AN:

261994

Other (OTH)

AF:

0.00318

AC:

AN:

22322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0137

AC:

2081

AN:

152054

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

983

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0474

AC:

1967

AN:

41464

American (AMR)

AF:

0.00504

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000195

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67990

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

113

227

340

454

567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0106

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.097

(source)

DANN

Benign

0.60

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over