Variant 6-138170717-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000251691.5(ARFGEF3):c.137+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,540,840 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.027 ( 80 hom., cov: 32)

Exomes 𝑓: 0.016 ( 230 hom. )

Consequence

ARFGEF3
ENST00000251691.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.00002275

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.36

Variant links:

Genes affected

ARFGEF3 (HGNC:21213): (ARFGEF family member 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in transport vesicle membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARFGEF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 6-138170717-G-A is Benign according to our data. Variant chr6-138170717-G-A is described in ClinVar as [Benign]. Clinvar id is 3041335.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF3	NM_020340.5 linkuse as main transcript	c.137+4G>A		splice_donor_region_variant, intron_variant		ENST00000251691.5	NP_065073.3
ARFGEF3	XR_001743524.2 linkuse as main transcript	n.285+4G>A		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF3	ENST00000251691.5 linkuse as main transcript	c.137+4G>A		splice_donor_region_variant, intron_variant		1	NM_020340.5	ENSP00000251691	P1

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4111

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0545

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00575

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0273

GnomAD3 exomes

AF:

0.0165

AC:

4068

AN:

246730

Hom.:

AF XY:

0.0160

AC XY:

2144

AN XY:

134006

show subpopulations

Gnomad AFR exome

AF:

0.0527

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.0393

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00494

Gnomad FIN exome

AF:

0.00679

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0158

AC:

21872

AN:

1388584

Hom.:

230

Cov.:

AF XY:

0.0156

AC XY:

10863

AN XY:

694858

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.0354

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00498

Gnomad4 FIN exome

AF:

0.00590

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0194

GnomAD4 genome

AF:

0.0270

AC:

4113

AN:

152256

Hom.:

Cov.:

AF XY:

0.0265

AC XY:

1974

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0544

Gnomad4 AMR

AF:

0.0221

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.00575

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0231

Hom.:

Bravo

AF:

0.0292

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0200

EpiControl

AF:

0.0195

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARFGEF3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.034

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