rs2253104

Positions:

• chr11-6479079-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376558.2(ARFIP2):​c.315+61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,588,842 control chromosomes in the GnomAD database, including 227,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25845 hom., cov: 31)
  • Exomes 𝑓: 0.52 (201539 hom.)
• Consequence: ARFIP2 NM_001376558.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

Genes affected

ARFIP2 (HGNC:17160): (ADP ribosylation factor interacting protein 2) Enables several functions, including GTP-dependent protein binding activity; membrane curvature sensor activity; and phosphatidylinositol-4-phosphate binding activity. Involved in actin cytoskeleton organization. Located in cell cortex; ruffle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFIP2	NM_001376558.2	c.315+61T>C		intron_variant		ENST00000396777.8	NP_001363487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFIP2	ENST00000396777.8	c.315+61T>C		intron_variant		2	NM_001376558.2	ENSP00000379998	P1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86446 AN: 151878 Hom.: 25817 Cov.: 31

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.524 AC: 752488 AN: 1436846 Hom.: 201539 Cov.: 28 AF XY: 0.522 AC XY: 373087 AN XY: 714330

Gnomad4 AFR exome AF: 0.738

Gnomad4 AMR exome AF: 0.608

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.569 AC: 86530 AN: 151996 Hom.: 25845 Cov.: 31 AF XY: 0.559 AC XY: 41509 AN XY: 74288

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.543

Alfa AF: 0.547 Hom.: 11038

Bravo AF: 0.586

Asia WGS AF: 0.340 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.32

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: rs2253104; hg19: chr11-6500309; COSMIC: COSV54446884; COSMIC: COSV54446884;