Genetic Variant ARFGAP2:c.*4G>A (chr11-47165478-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_032389.6(ARFGAP2):c.*4G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,567,532 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0075 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 25 hom. )

Consequence

ARFGAP2
NM_032389.6 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.551

Publications

0 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-47165478-C-T is Benign according to our data. Variant chr11-47165478-C-T is described in ClinVar as Benign. ClinVar VariationId is 3038983.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00748 (1130/151068) while in subpopulation AFR AF = 0.0259 (1063/41018). AF 95% confidence interval is 0.0246. There are 8 homozygotes in GnomAd4. There are 543 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARFGAP2	NM_032389.6	MANE Select	c.*4G>A	3_prime_UTR	Exon 16 of 16	NP_115765.2
ARFGAP2	NM_001410995.1		c.*4G>A	3_prime_UTR	Exon 17 of 17	NP_001397924.1	E9PN48
ARFGAP2	NM_001242832.2		c.*4G>A	3_prime_UTR	Exon 15 of 15	NP_001229761.1	G5E9L0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARFGAP2	ENST00000524782.6	TSL:1 MANE Select	c.*4G>A	3_prime_UTR	Exon 16 of 16	ENSP00000434442.1	Q8N6H7-1
ARFGAP2	ENST00000892878.1		c.*4G>A	3_prime_UTR	Exon 17 of 17	ENSP00000562937.1
ARFGAP2	ENST00000946556.1		c.*4G>A	3_prime_UTR	Exon 17 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

1126

AN:

150958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00265

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00434

GnomAD2 exomes

AF:

0.00196

AC:

427

AN:

217592

AF XY:

0.00128

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.000328

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000609

GnomAD4 exome

AF:

0.000945

AC:

1339

AN:

1416464

Hom.:

Cov.:

AF XY:

0.000841

AC XY:

592

AN XY:

704236

show subpopulations

African (AFR)

AF:

0.0285

AC:

879

AN:

30830

American (AMR)

AF:

0.00163

AC:

AN:

39250

Ashkenazi Jewish (ASJ)

AF:

0.000639

AC:

AN:

25032

East Asian (EAS)

AF:

0.0000273

AC:

AN:

36620

South Asian (SAS)

AF:

0.000522

AC:

AN:

80466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52562

Middle Eastern (MID)

AF:

0.00288

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

0.000193

AC:

210

AN:

1088010

Other (OTH)

AF:

0.00191

AC:

111

AN:

58130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

123

184

246

307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00748

AC:

1130

AN:

151068

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

543

AN XY:

73702

show subpopulations

African (AFR)

AF:

0.0259

AC:

1063

AN:

41018

American (AMR)

AF:

0.00264

AC:

AN:

15140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.000417

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10320

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67900

Other (OTH)

AF:

0.00430

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00682

Hom.:

Bravo

AF:

0.00846

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARFGAP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.8

(source)

DANN

Benign

0.81

PhyloP100

-0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over