chr10-88935065-C-T

Variant names:

• chr10-88935065-C-T
• rs367977687
• ENST00000713597.1:c.*158G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000713597.1(ACTA2):​c.*158G>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 0.000178 in 1,061,516 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: ACTA2 ENST00000713597.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.01
• Publications: 0 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=-0.79).
• BP6: Variant 10-88935065-C-T is Benign according to our data. Variant chr10-88935065-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 368929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000191 (29/152128) while in subpopulation EAS AF = 0.00193 (10/5168). AF 95% confidence interval is 0.00105. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 29 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTA2-AS1	NR_125373.1		n.690C>T		non_coding_transcript_exon	Exon 3 of 5
	ACTA2	NM_001613.4	MANE Select	c.*158G>A		downstream_gene	N/A	NP_001604.1	P62736
	ACTA2	NM_001141945.3		c.*158G>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.*158G>A		3_prime_UTR	Exon 10 of 10	ENSP00000518893.1	P62736
	STAMBPL1	ENST00000371927.7	TSL:2	c.1254+12629C>T		intron	N/A	ENSP00000360995.3	Q96FJ0-2
	ACTA2-AS1	ENST00000437930.4	TSL:2	n.731C>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.000176 AC: 160 AN: 909388 Hom.: 1 Cov.: 12 AF XY: 0.000218 AC XY: 101 AN XY: 462656

African (AFR) AF: 0.000183 AC: 4 AN: 21824

American (AMR) AF: 0.000116 AC: 4 AN: 34588

Ashkenazi Jewish (ASJ) AF: 0.0000575 AC: 1 AN: 17380

East Asian (EAS) AF: 0.00118 AC: 40 AN: 33888

South Asian (SAS) AF: 0.000557 AC: 36 AN: 64596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37970

Middle Eastern (MID) AF: 0.00430 AC: 12 AN: 2790

European-Non Finnish (NFE) AF: 0.0000747 AC: 49 AN: 655976

Other (OTH) AF: 0.000347 AC: 14 AN: 40376

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74380

African (AFR) AF: 0.000313 AC: 13 AN: 41506

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5168

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68000

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000193

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	Moyamoya disease (1)
-	-	1	Multisystemic smooth muscle dysfunction syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.18
DANN	Benign	0.82
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs367977687; hg19: chr10-90694822;