chr20-48946189-A-G

Position:

• chr20-48946189-A-G

Variant summary

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

The NM_006420.3(ARFGEF2):​c.276+4202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,118 control chromosomes in the GnomAD database, including 5,266 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 0.25 (5266 hom., cov: 32)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF2	NM_006420.3	c.276+4202A>G		intron_variant		ENST00000371917.5	NP_006411.2
ARFGEF2	NM_001410846.1	c.276+4202A>G		intron_variant			NP_001397775.1
ARFGEF2	XM_047439832.1	c.-288-5134A>G		intron_variant			XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.276+4202A>G		intron_variant		1	NM_006420.3	ENSP00000360985.4

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37399 AN: 152000 Hom.: 5261 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.246 AC: 37417 AN: 152118 Hom.: 5266 Cov.: 32 AF XY: 0.255 AC XY: 18968 AN XY: 74348

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.272

Alfa AF: 0.266 Hom.: 2614

Bravo AF: 0.248

Asia WGS AF: 0.382 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.38

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: rs6019548; hg19: chr20-47562726;