rs1115535

Positions:

• chr20-48974027-T-C

Variant summary

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

The NM_006420.3(ARFGEF2):​c.1666-739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,052 control chromosomes in the GnomAD database, including 3,068 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 0.18 (3068 hom., cov: 31)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

ARFGEF2 (HGNC:15853): (ADP ribosylation factor guanine nucleotide exchange factor 2) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARFGEF2	NM_006420.3	c.1666-739T>C		intron_variant		ENST00000371917.5
ARFGEF2	NM_001410846.1	c.1663-739T>C		intron_variant
ARFGEF2	XM_047439832.1	c.1102-739T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.1666-739T>C		intron_variant		1	NM_006420.3	P4

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26630 AN: 151936 Hom.: 3067 Cov.: 31

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.0908

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26632 AN: 152052 Hom.: 3068 Cov.: 31 AF XY: 0.170 AC XY: 12624 AN XY: 74330

Gnomad4 AFR AF: 0.0453

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0508

Gnomad4 SAS AF: 0.0915

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.151

Alfa AF: 0.236 Hom.: 5738

Bravo AF: 0.164

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.65

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: rs1115535; hg19: chr20-47590564;