Genetic Variant NM_032389.6:c.1232G>A (chr11-47166860-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.835

Publications

49 publications found

Variant links:

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]

ARFGAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFGAP2	NM_032389.6 link	c.1232G>A	p.Ser411Asn	missense_variant	Exon 13 of 16	ENST00000524782.6	NP_115765.2	Q8N6H7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFGAP2	ENST00000524782.6 link	c.1232G>A	p.Ser411Asn	missense_variant	Exon 13 of 16	1	NM_032389.6	ENSP00000434442.1		Q8N6H7-1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58389

AN:

152008

Hom.:

12950

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.323

AC XY:

234695

AN XY:

727062

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

17694

35388

53082

70776

88470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11692

23384

35076

46768

58460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.384

AC:

58441

AN:

152126

Hom.:

12961

Cov.:

AF XY:

0.378

AC XY:

28137

AN XY:

74380

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21722

AN:

67944

Other (OTH)

AF:

0.355

AC:

751

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1710

3420

5129

6839

8549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.019

.;T;T;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.55

T;T;T;T

MetaRNN

Benign

0.000017

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;.;L;.

PhyloP100

0.83

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.57

.;.;N;N

REVEL

Benign

0.054

Sift

Benign

0.63

.;.;T;T

Sift4G

Benign

0.54

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.078

MPC

0.21

ClinPred

0.00078

GERP RS

3.8

Varity_R

0.027

gMVP

0.19

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over