11-47165493-C-T

Variant names:

• chr11-47165493-C-T
• rs142683966
• NM_032389.6:c.1555G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_032389.6(ARFGAP2):​c.1555G>A​(p.Gly519Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0054 in 1,569,028 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0032 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (30 hom.)
• Consequence: ARFGAP2 NM_032389.6 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.67
• Publications: 6 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009077549).
• BP6: Variant 11-47165493-C-T is Benign according to our data. Variant chr11-47165493-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3044117.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 4 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.1555G>A	p.Gly519Ser	missense	Exon 16 of 16	NP_115765.2
	ARFGAP2	NM_001410995.1		c.1597G>A	p.Gly533Ser	missense	Exon 17 of 17	NP_001397924.1	E9PN48
	ARFGAP2	NM_001242832.2		c.1471G>A	p.Gly491Ser	missense	Exon 15 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.1555G>A	p.Gly519Ser	missense	Exon 16 of 16	ENSP00000434442.1	Q8N6H7-1
	ARFGAP2	ENST00000892878.1		c.1672G>A	p.Gly558Ser	missense	Exon 17 of 17	ENSP00000562937.1
	ARFGAP2	ENST00000946556.1		c.1642G>A	p.Gly548Ser	missense	Exon 17 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 480 AN: 150892 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00403

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00532

Gnomad OTH AF: 0.00145

GnomAD2 exomes AF: 0.00304 AC: 622 AN: 204746 AF XY: 0.00299

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00126

Gnomad NFE exome AF: 0.00485

Gnomad OTH exome AF: 0.00486

GnomAD4 exome AF: 0.00564 AC: 7997 AN: 1418020 Hom.: 30 Cov.: 29 AF XY: 0.00542 AC XY: 3826 AN XY: 705474

African (AFR) AF: 0.00118 AC: 36 AN: 30522

American (AMR) AF: 0.00319 AC: 123 AN: 38558

Ashkenazi Jewish (ASJ) AF: 0.0000801 AC: 2 AN: 24960

East Asian (EAS) AF: 0.0000541 AC: 2 AN: 36992

South Asian (SAS) AF: 0.000236 AC: 19 AN: 80450

European-Finnish (FIN) AF: 0.00156 AC: 82 AN: 52574

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5570

European-Non Finnish (NFE) AF: 0.00681 AC: 7424 AN: 1090202

Other (OTH) AF: 0.00529 AC: 308 AN: 58192

GnomAD4 genome AF: 0.00317 AC: 479 AN: 151008 Hom.: 4 Cov.: 32 AF XY: 0.00289 AC XY: 213 AN XY: 73742

African (AFR) AF: 0.00100 AC: 41 AN: 40864

American (AMR) AF: 0.00403 AC: 61 AN: 15152

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

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5136

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4788

European-Finnish (FIN) AF: 0.00105 AC: 11 AN: 10442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00530 AC: 360 AN: 67862

Other (OTH) AF: 0.00143 AC: 3 AN: 2098

Alfa AF: 0.00430 Hom.: 3

Bravo AF: 0.00361

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00558 AC: 48

ExAC AF: 0.00288 AC: 350

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	0.18
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.094
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.98	D
Vest4		0.35
MVP		0.33
MPC		0.34
ClinPred		0.021	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.60
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs142683966; hg19: chr11-47187044;