rs1254836237

Variant names:

• chr10-88947270-G-A
• rs1254836237
• NM_001613.4:c.246C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-88947270-G-A
• chr10-88947270-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001613.4(ACTA2):​c.246C>T​(p.Asp82Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: ACTA2 NM_001613.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.285
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 10-88947270-G-A is Benign according to our data. Variant chr10-88947270-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 919374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.285 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 38 AD,Unknown gene.

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.246C>T	p.Asp82Asp	synonymous	Exon 3 of 9	NP_001604.1	P62736
	ACTA2	NM_001141945.3		c.246C>T	p.Asp82Asp	synonymous	Exon 3 of 9	NP_001135417.1	D2JYH4
	ACTA2	NM_001320855.2		c.246C>T	p.Asp82Asp	synonymous	Exon 3 of 9	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.246C>T	p.Asp82Asp	synonymous	Exon 3 of 9	ENSP00000224784.6	P62736
	ACTA2	ENST00000713598.1		c.246C>T	p.Asp82Asp	synonymous	Exon 3 of 9	ENSP00000518894.1	A0AAQ5BGG5
	ACTA2	ENST00000415557.2	TSL:3	c.246C>T	p.Asp82Asp	synonymous	Exon 3 of 9	ENSP00000396730.2	P62736

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152038 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1461672 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 727128

African (AFR) AF: 0.0000598 AC: 2 AN: 33462

American (AMR) AF: 0.0000447 AC: 2 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111866

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152038 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74266

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Familial thoracic aortic aneurysm and aortic dissection (3)
-	-	1	Aortic aneurysm, familial thoracic 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		-0.28
Mutation Taster		=95/5	polymorphism

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: rs1254836237; hg19: chr10-90707027; COSMIC: COSV56516099; COSMIC: COSV56516099;