Variant rs41304647 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006420.3(ARFGEF2):c.424-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 1,613,286 control chromosomes in the GnomAD database, including 3,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 191 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3076 hom. )

Consequence

ARFGEF2
NM_006420.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.60

Variant links:

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]

ARFGEF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 20-48952689-C-T is Benign according to our data. Variant chr20-48952689-C-T is described in ClinVar as [Benign]. Clinvar id is 136418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-48952689-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ARFGEF2	NM_006420.3 linkuse as main transcript	c.424-16C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000371917.5	NP_006411.2
ARFGEF2	NM_001410846.1 linkuse as main transcript	c.424-16C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001397775.1
ARFGEF2	XM_047439832.1 linkuse as main transcript	c.-141-16C>T	splice_polypyrimidine_tract_variant, intron_variant		XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917.5 linkuse as main transcript	c.424-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006420.3	ENSP00000360985	P4

Frequencies

GnomAD3 genomes

AF:

0.0473

AC:

7192

AN:

152136

Hom.:

192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0951

Gnomad EAS

AF:

0.0813

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0347

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.0533

GnomAD3 exomes

AF:

0.0599

AC:

15054

AN:

251388

Hom.:

591

AF XY:

0.0652

AC XY:

8854

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.0935

Gnomad EAS exome

AF:

0.0694

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0334

Gnomad NFE exome

AF:

0.0635

Gnomad OTH exome

AF:

0.0653

GnomAD4 exome

AF:

0.0611

AC:

89264

AN:

1461032

Hom.:

3076

Cov.:

AF XY:

0.0632

AC XY:

45971

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.0263

Gnomad4 ASJ exome

AF:

0.0910

Gnomad4 EAS exome

AF:

0.0570

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.0358

Gnomad4 NFE exome

AF:

0.0606

Gnomad4 OTH exome

AF:

0.0615

GnomAD4 genome

AF:

0.0472

AC:

7192

AN:

152254

Hom.:

191

Cov.:

AF XY:

0.0466

AC XY:

3472

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.0386

Gnomad4 ASJ

AF:

0.0951

Gnomad4 EAS

AF:

0.0815

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0347

Gnomad4 NFE

AF:

0.0637

Gnomad4 OTH

AF:

0.0546

Alfa

AF:

0.0603

Hom.:

Bravo

AF:

0.0448

Asia WGS

AF:

0.0640

AC:

223

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2013	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0080

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over