rs6012564

Positions:

• chr20-48925063-G-A
• chr20-48925063-G-C

Variant summary

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

The NM_006420.3(ARFGEF2):​c.121+3053G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,036 control chromosomes in the GnomAD database, including 29,163 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 0.62 (29163 hom., cov: 32)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF2	NM_006420.3	c.121+3053G>A		intron_variant		ENST00000371917.5	NP_006411.2
ARFGEF2	NM_001410846.1	c.121+3053G>A		intron_variant			NP_001397775.1
ARFGEF2	XM_047439832.1	c.-289+3053G>A		intron_variant			XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.121+3053G>A		intron_variant		1	NM_006420.3	ENSP00000360985	P4

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93832 AN: 151918 Hom.: 29129 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.618 AC: 93919 AN: 152036 Hom.: 29163 Cov.: 32 AF XY: 0.619 AC XY: 45953 AN XY: 74280

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.592

Alfa AF: 0.597 Hom.: 13558

Bravo AF: 0.623

Asia WGS AF: 0.653 AC: 2272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.74
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: rs6012564; hg19: chr20-47541600;