rs6019566

chr20-48974545-C-Achr20-48974545-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006420.3(ARFGEF2):c.1666-221C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,920 control chromosomes in the GnomAD database, including 1,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1688 hom., cov: 31)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 20-48974545-C-A is Benign according to our data. Variant chr20-48974545-C-A is described in ClinVar as [Benign]. Clinvar id is 679355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARFGEF2	NM_006420.3	c.1666-221C>A		intron_variant		ENST00000371917.5
ARFGEF2	NM_001410846.1	c.1663-221C>A		intron_variant
ARFGEF2	XM_047439832.1	c.1102-221C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.1666-221C>A		intron_variant		1	NM_006420.3	P4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19100 AN: 151802 Hom.: 1683 Cov.: 31

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.126 AC: 19125 AN: 151920 Hom.: 1688 Cov.: 31 AF XY: 0.135 AC XY: 10000 AN XY: 74220

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.136

Alfa AF: 0.113 Hom.: 1375

Bravo AF: 0.133

Asia WGS AF: 0.268 AC: 933 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	5.8
Dann	Benign	0.67

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: rs6019566; hg19: chr20-47591082;