rs143018690

Variant names:

• chr3-195291722-C-T
• rs143018690
• NM_012287.6:c.2047G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-195291722-C-T
• chr3-195291722-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012287.6(ACAP2):​c.2047G>A​(p.Val683Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000333 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: ACAP2 NM_012287.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 2 publications found

Genes affected

ACAP2 (HGNC:16469): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 2) Enables GTPase activator activity. Acts upstream of or within actin filament-based process. Located in ruffle. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000295476 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07994202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012287.6. 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
	ACAP2	NM_012287.6	MANE Select	c.2047G>A	p.Val683Ile	missense	Exon 20 of 23	NP_036419.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAP2	ENST00000326793.11	TSL:1 MANE Select	c.2047G>A	p.Val683Ile	missense	Exon 20 of 23	ENSP00000324287.6	Q15057
	ACAP2	ENST00000867120.1		c.2236G>A	p.Val746Ile	missense	Exon 22 of 25	ENSP00000537179.1
	ACAP2	ENST00000867114.1		c.2152G>A	p.Val718Ile	missense	Exon 21 of 24	ENSP00000537173.1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.000426

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 250846 AF XY: 0.000118

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000346 AC: 506 AN: 1461374 Hom.: 0 Cov.: 30 AF XY: 0.000314 AC XY: 228 AN XY: 727002

African (AFR) AF: 0.000149 AC: 5 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000435 AC: 484 AN: 1111788

Other (OTH) AF: 0.000282 AC: 17 AN: 60378

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74476

African (AFR) AF: 0.0000481 AC: 2 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000387 Hom.: 0

Bravo AF: 0.000212

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Benign	0.27
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.0087
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.62	N
PhyloP100		3.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.046
Sift	Benign	0.94	T
Sift4G	Benign	0.50	T
Polyphen		0.0070	B
Vest4		0.23
MVP		0.38
MPC		0.52
ClinPred		0.064	T
GERP RS		5.7
Varity_R		0.094
gMVP		0.054
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143018690; hg19: chr3-195012451;