Variant 20-48941832-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006420.3(ARFGEF2):c.153-32C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000668 in 1,614,120 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 5 hom. )

Consequence

ARFGEF2
NM_006420.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00200

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=-0.8).

BP6

Variant 20-48941832-C-A is Benign according to our data. Variant chr20-48941832-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1217561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00348 (530/152324) while in subpopulation AFR AF= 0.0115 (476/41568). AF 95% confidence interval is 0.0106. There are 5 homozygotes in gnomad4. There are 262 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ARFGEF2	NM_006420.3 linkuse as main transcript	c.153-32C>A	intron_variant	ENST00000371917.5
ARFGEF2	NM_001410846.1 linkuse as main transcript	c.153-32C>A	intron_variant
ARFGEF2	XM_047439832.1 linkuse as main transcript	c.-288-9491C>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARFGEF2	ENST00000371917.5 linkuse as main transcript	c.153-32C>A		intron_variant		1	NM_006420.3	P4

Frequencies

GnomAD3 genomes

AF:

0.00336

AC:

512

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000760

AC:

191

AN:

251448

Hom.:

AF XY:

0.000618

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00991

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000376

AC:

549

AN:

1461796

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

244

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0115

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00348

AC:

530

AN:

152324

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000254

Hom.:

Bravo

AF:

0.00351

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 12, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.2

DANN

Benign

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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