11-47168177-C-T

Variant names:

• chr11-47168177-C-T
• rs34662994
• NM_032389.6:c.1016G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_032389.6(ARFGAP2):​c.1016G>A​(p.Arg339His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,614,238 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R339L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0062 (13 hom., cov: 31)
  • Exomes 𝑓: 0.00075 (7 hom.)
• Consequence: ARFGAP2 NM_032389.6 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.30
• Publications: 10 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]

ENSG00000270060 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008449376).
• BP6: Variant 11-47168177-C-T is Benign according to our data. Variant chr11-47168177-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055789.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0062 (944/152346) while in subpopulation AFR AF = 0.0217 (902/41580). AF 95% confidence interval is 0.0205. There are 13 homozygotes in GnomAd4. There are 451 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 gene

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.1016G>A	p.Arg339His	missense	Exon 11 of 16	NP_115765.2
	ARFGAP2	NM_001410995.1		c.1058G>A	p.Arg353His	missense	Exon 12 of 17	NP_001397924.1	E9PN48
	ARFGAP2	NM_001242832.2		c.932G>A	p.Arg311His	missense	Exon 10 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.1016G>A	p.Arg339His	missense	Exon 11 of 16	ENSP00000434442.1	Q8N6H7-1
	ARFGAP2	ENST00000892878.1		c.1133G>A	p.Arg378His	missense	Exon 12 of 17	ENSP00000562937.1
	ARFGAP2	ENST00000946556.1		c.1103G>A	p.Arg368His	missense	Exon 12 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes AF: 0.00619 AC: 943 AN: 152228 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00169 AC: 426 AN: 251462 AF XY: 0.00100

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000749 AC: 1095 AN: 1461892 Hom.: 7 Cov.: 33 AF XY: 0.000609 AC XY: 443 AN XY: 727248

African (AFR) AF: 0.0253 AC: 848 AN: 33480

American (AMR) AF: 0.00123 AC: 55 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000880 AC: 23 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1112012

Other (OTH) AF: 0.00179 AC: 108 AN: 60396

GnomAD4 genome AF: 0.00620 AC: 944 AN: 152346 Hom.: 13 Cov.: 31 AF XY: 0.00605 AC XY: 451 AN XY: 74496

African (AFR) AF: 0.0217 AC: 902 AN: 41580

American (AMR) AF: 0.00163 AC: 25 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00159 Hom.: 2

Bravo AF: 0.00718

ESP6500AA AF: 0.0191 AC: 84

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00201 AC: 244

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ARFGAP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.74
MVP		0.41
MPC		0.89
ClinPred		0.038	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.33
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34662994; hg19: chr11-47189728;