rs714887

Variant names:

• chr10-88941888-A-G
• rs714887
• NM_001613.4:c.370-19T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-88941888-A-G
• chr10-88941888-A-T

Variant summary

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

The NM_001613.4(ACTA2):​c.370-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 1,601,224 control chromosomes in the GnomAD database, including 8,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (765 hom., cov: 32)
  • Exomes 𝑓: 0.087 (8122 hom.)
• Consequence: ACTA2 NM_001613.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.729
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 10-88941888-A-G is Benign according to our data. Variant chr10-88941888-A-G is described in ClinVar as Benign. ClinVar VariationId is 136279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTA2	NM_001613.4	MANE Select	c.370-19T>C		intron	N/A	NP_001604.1	P62736
	ACTA2	NM_001141945.3		c.370-19T>C		intron	N/A	NP_001135417.1	D2JYH4
	ACTA2	NM_001320855.2		c.370-19T>C		intron	N/A	NP_001307784.1	P62736

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTA2	ENST00000224784.10	TSL:1 MANE Select	c.370-19T>C		intron	N/A	ENSP00000224784.6	P62736
	ACTA2	ENST00000713598.1		c.393T>C	p.Ala131Ala	synonymous	Exon 5 of 9	ENSP00000518894.1	A0AAQ5BGG5
	STAMBPL1	ENST00000371927.7	TSL:2	c.1254+19452A>G		intron	N/A	ENSP00000360995.3	Q96FJ0-2

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13497 AN: 152096 Hom.: 762 Cov.: 32

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.0455

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.120 AC: 27865 AN: 231922 AF XY: 0.127

Gnomad AFR exome AF: 0.0786

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.278

Gnomad FIN exome AF: 0.0529

Gnomad NFE exome AF: 0.0692

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0872 AC: 126402 AN: 1449010 Hom.: 8122 Cov.: 31 AF XY: 0.0926 AC XY: 66633 AN XY: 719880

African (AFR) AF: 0.0769 AC: 2557 AN: 33258

American (AMR) AF: 0.114 AC: 4932 AN: 43302

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3724 AN: 25856

East Asian (EAS) AF: 0.255 AC: 9999 AN: 39244

South Asian (SAS) AF: 0.272 AC: 22984 AN: 84550

European-Finnish (FIN) AF: 0.0532 AC: 2804 AN: 52690

Middle Eastern (MID) AF: 0.127 AC: 732 AN: 5748

European-Non Finnish (NFE) AF: 0.0654 AC: 72284 AN: 1104438

Other (OTH) AF: 0.107 AC: 6386 AN: 59924

GnomAD4 genome AF: 0.0887 AC: 13505 AN: 152214 Hom.: 765 Cov.: 32 AF XY: 0.0940 AC XY: 6997 AN XY: 74424

African (AFR) AF: 0.0768 AC: 3188 AN: 41528

American (AMR) AF: 0.111 AC: 1701 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3466

East Asian (EAS) AF: 0.267 AC: 1380 AN: 5178

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4818

European-Finnish (FIN) AF: 0.0455 AC: 483 AN: 10612

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0681 AC: 4634 AN: 68004

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.0812 Hom.: 203

Bravo AF: 0.0891

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Aortic aneurysm, familial thoracic 6 (1)
-	-	1	not provided (1)
-	-	1	Thoracic aortic aneurysm (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs714887; hg19: chr10-90701645; COSMIC: COSV56517790; COSMIC: COSV56517790;