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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFGAP2	NM_032389.6 link	c.*4G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000524782.6	NP_115765.2	Q8N6H7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFGAP2	ENST00000524782 link	c.*4G>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_032389.6	ENSP00000434442.1		Q8N6H7-1

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

GnomAD3 exomes

AF:

0.00196

AC:

427

AN:

217592

Hom.:

AF XY:

0.00128

AC XY:

152

AN XY:

118834

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 SAS exome

AF:

0.000458

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

Gnomad4 AFR exome

AF:

0.0285

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.000639

Gnomad4 EAS exome

AF:

0.0000273

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000193

Gnomad4 OTH exome

AF:

0.00191

GnomAD4 genome

AF:

0.00748

AC:

1130

AN:

151068

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

543

AN XY:

73702

show subpopulations

Gnomad4 AFR

AF:

0.0259

Gnomad4 AMR

AF:

0.00264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00430

Alfa

AF:

0.00445

Hom.:

Bravo

AF:

0.00846

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARFGAP2-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.8

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over