10-88935036-G-T

Variant names:

• chr10-88935036-G-T
• rs7908852
• ENST00000713597.1:c.*187C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000713597.1(ACTA2):​c.*187C>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 0.0215 in 732,328 control chromosomes in the GnomAD database, including 529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (127 hom., cov: 32)
  • Exomes 𝑓: 0.020 (402 hom.)
• Consequence: ACTA2 ENST00000713597.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.69
• Publications: 1 publications found

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]

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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-88935036-G-T is Benign according to our data. Variant chr10-88935036-G-T is described in ClinVar as Benign. ClinVar VariationId is 1278133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTA2-AS1	NR_125373.1		n.661G>T		non_coding_transcript_exon	Exon 3 of 5
	ACTA2	NM_001613.4	MANE Select	c.*187C>A		downstream_gene	N/A	NP_001604.1	P62736
	ACTA2	NM_001141945.3		c.*187C>A		downstream_gene	N/A	NP_001135417.1	D2JYH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTA2	ENST00000713597.1		c.*187C>A		3_prime_UTR	Exon 10 of 10	ENSP00000518893.1	P62736
	STAMBPL1	ENST00000371927.7	TSL:2	c.1254+12600G>T		intron	N/A	ENSP00000360995.3	Q96FJ0-2
	ACTA2-AS1	ENST00000437930.4	TSL:2	n.702G>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4187 AN: 152046 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00903

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0198 AC: 11508 AN: 580164 Hom.: 402 Cov.: 8 AF XY: 0.0206 AC XY: 6244 AN XY: 303018

African (AFR) AF: 0.0533 AC: 809 AN: 15178

American (AMR) AF: 0.00837 AC: 204 AN: 24370

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 719 AN: 13502

East Asian (EAS) AF: 0.138 AC: 3902 AN: 28362

South Asian (SAS) AF: 0.0349 AC: 1871 AN: 53682

European-Finnish (FIN) AF: 0.00221 AC: 64 AN: 28894

Middle Eastern (MID) AF: 0.0171 AC: 35 AN: 2046

European-Non Finnish (NFE) AF: 0.00843 AC: 3247 AN: 385306

Other (OTH) AF: 0.0228 AC: 657 AN: 28824

GnomAD4 genome AF: 0.0276 AC: 4205 AN: 152164 Hom.: 127 Cov.: 32 AF XY: 0.0280 AC XY: 2083 AN XY: 74390

African (AFR) AF: 0.0539 AC: 2239 AN: 41504

American (AMR) AF: 0.00987 AC: 151 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3468

East Asian (EAS) AF: 0.139 AC: 713 AN: 5148

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4828

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10604

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00903 AC: 614 AN: 67998

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0137 Hom.: 36

Bravo AF: 0.0297

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0090
DANN	Benign	0.59
PhyloP100		-4.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7908852; hg19: chr10-90694793;