11-47171658-A-G

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.809+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,720 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (7 hom.)
• Consequence: ARFGAP2 NM_032389.6 splice_donor_region, intron
• Scores: Splicing: ADA: 0.006097
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60

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=-0.82).
• BP6: Variant 11-47171658-A-G is Benign according to our data. Variant chr11-47171658-A-G is described in ClinVar as [Benign]. Clinvar id is 3055614.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00592 (901/152250) while in subpopulation AFR AF= 0.0208 (864/41534). AF 95% confidence interval is 0.0197. There are 10 homozygotes in gnomad4. There are 423 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARFGAP2	NM_032389.6	c.809+6T>C		splice_donor_region_variant, intron_variant		ENST00000524782.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARFGAP2	ENST00000524782.6	c.809+6T>C		splice_donor_region_variant, intron_variant		1	NM_032389.6	A1

Frequencies

GnomAD3 genomes AF: 0.00592 AC: 900 AN: 152132 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00164 AC: 411 AN: 251088 Hom.: 6 AF XY: 0.000958 AC XY: 130 AN XY: 135734

Gnomad AFR exome AF: 0.0221

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000718 AC: 1049 AN: 1461470 Hom.: 7 Cov.: 30 AF XY: 0.000586 AC XY: 426 AN XY: 727052

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.000880

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000342

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00592 AC: 901 AN: 152250 Hom.: 10 Cov.: 32 AF XY: 0.00568 AC XY: 423 AN XY: 74438

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00305 Hom.: 3

Bravo AF: 0.00689

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Jul 12, 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	-0.82
Cadd	Benign	10
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0061
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.010		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: rs114371790; hg19: chr11-47193209;