11-47165478-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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 (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (25 hom.)
• Consequence: ARFGAP2 NM_032389.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.551

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

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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 GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARFGAP2	NM_032389.6	c.*4G>A		3_prime_UTR_variant	16/16	ENST00000524782.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARFGAP2	ENST00000524782.6	c.*4G>A		3_prime_UTR_variant	16/16	1	NM_032389.6	A1

Frequencies

GnomAD3 genomes AF: 0.00746 AC: 1126 AN: 150958 Hom.: 8 Cov.: 32

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.: 9 AF XY: 0.00128 AC XY: 152 AN XY: 118834

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.: 25 Cov.: 29 AF XY: 0.000841 AC XY: 592 AN XY: 704236

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.: 8 Cov.: 32 AF XY: 0.00737 AC XY: 543 AN XY: 73702

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.: 3

Bravo AF: 0.00846

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ARFGAP2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

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

Other links and lift over

dbSNP: rs138370539; hg19: chr11-47187029;