rs3740691

Variant names:

• chr11-47166860-C-T
• rs3740691
• NM_032389.6:c.1232G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032389.6(ARFGAP2):​c.1232G>A​(p.Ser411Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,628 control chromosomes in the GnomAD database, including 92,130 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (12961 hom., cov: 33)
  • Exomes 𝑓: 0.32 (79169 hom.)
• Consequence: ARFGAP2 NM_032389.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.835
• Publications: 49 publications found

Genes affected

ARFGAP2 (HGNC:13504): (ADP ribosylation factor GTPase activating protein 2) Predicted to enable GTPase activator activity. Predicted to be involved in COPI coating of Golgi vesicle. Located in Golgi apparatus; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.73986E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032389.6. 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
	ARFGAP2	NM_032389.6	MANE Select	c.1232G>A	p.Ser411Asn	missense	Exon 13 of 16	NP_115765.2
	ARFGAP2	NM_001410995.1		c.1274G>A	p.Ser425Asn	missense	Exon 14 of 17	NP_001397924.1	E9PN48
	ARFGAP2	NM_001242832.2		c.1148G>A	p.Ser383Asn	missense	Exon 12 of 15	NP_001229761.1	G5E9L0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGAP2	ENST00000524782.6	TSL:1 MANE Select	c.1232G>A	p.Ser411Asn	missense	Exon 13 of 16	ENSP00000434442.1	Q8N6H7-1
	ARFGAP2	ENST00000892878.1		c.1349G>A	p.Ser450Asn	missense	Exon 14 of 17	ENSP00000562937.1
	ARFGAP2	ENST00000946556.1		c.1319G>A	p.Ser440Asn	missense	Exon 14 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58389 AN: 152008 Hom.: 12950 Cov.: 33

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.309 AC: 77573 AN: 251040 AF XY: 0.314

Gnomad AFR exome AF: 0.628

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.126

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.324

Gnomad OTH exome AF: 0.328

GnomAD4 exome AF: 0.321 AC: 469179 AN: 1461502 Hom.: 79169 Cov.: 41 AF XY: 0.323 AC XY: 234695 AN XY: 727062

African (AFR) AF: 0.627 AC: 20997 AN: 33478

American (AMR) AF: 0.187 AC: 8349 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 8145 AN: 26126

East Asian (EAS) AF: 0.115 AC: 4581 AN: 39696

South Asian (SAS) AF: 0.390 AC: 33609 AN: 86250

European-Finnish (FIN) AF: 0.230 AC: 12235 AN: 53156

Middle Eastern (MID) AF: 0.349 AC: 2011 AN: 5766

European-Non Finnish (NFE) AF: 0.323 AC: 359216 AN: 1111922

Other (OTH) AF: 0.332 AC: 20036 AN: 60390

GnomAD4 genome AF: 0.384 AC: 58441 AN: 152126 Hom.: 12961 Cov.: 33 AF XY: 0.378 AC XY: 28137 AN XY: 74380

African (AFR) AF: 0.616 AC: 25546 AN: 41500

American (AMR) AF: 0.278 AC: 4243 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3472

East Asian (EAS) AF: 0.130 AC: 673 AN: 5174

South Asian (SAS) AF: 0.388 AC: 1871 AN: 4824

European-Finnish (FIN) AF: 0.221 AC: 2346 AN: 10600

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21722 AN: 67944

Other (OTH) AF: 0.355 AC: 751 AN: 2116

Alfa AF: 0.340 Hom.: 27869

Bravo AF: 0.392

TwinsUK AF: 0.324 AC: 1201

ALSPAC AF: 0.326 AC: 1255

ESP6500AA AF: 0.613 AC: 2697

ESP6500EA AF: 0.317 AC: 2729

ExAC AF: 0.325 AC: 39436

Asia WGS AF: 0.326 AC: 1132 AN: 3478

EpiCase AF: 0.335

EpiControl AF: 0.339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.000017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.83
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.054
Sift	Benign	0.63	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.078
MPC		0.21
ClinPred		0.00078	T
GERP RS		3.8
Varity_R		0.027
gMVP		0.19
Mutation Taster		=99/1	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: rs3740691; hg19: chr11-47188411; COSMIC: COSV53563682; COSMIC: COSV53563682;