Variant 1-228097631-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001658.4(ARF1):c.300G>A(p.Val100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ARF1
NM_001658.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.07

Variant links:

Genes affected

ARF1 (HGNC:652): (ADP ribosylation factor 1) ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking as activators of phospholipase D. The gene products, including 6 ARF proteins and 11 ARF-like proteins, constitute a family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2 and ARF3), class II (ARF4 and ARF5) and class III (ARF6), and members of each class share a common gene organization. The ARF1 protein is localized to the Golgi apparatus and has a central role in intra-Golgi transport. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ARF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-228097631-G-A is Benign according to our data. Variant chr1-228097631-G-A is described in ClinVar as [Benign]. Clinvar id is 3040638.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.08 with no splicing effect.

BS2

High AC in GnomAd4 at 367 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARF1	NM_001658.4 linkuse as main transcript	c.300G>A	p.Val100=	synonymous_variant	4/5	ENST00000272102.10	NP_001649.1
ARF1	NM_001024226.2 linkuse as main transcript	c.300G>A	p.Val100=	synonymous_variant	4/5		NP_001019397.1
ARF1	NM_001024227.1 linkuse as main transcript	c.300G>A	p.Val100=	synonymous_variant	4/5		NP_001019398.1
ARF1	NM_001024228.2 linkuse as main transcript	c.300G>A	p.Val100=	synonymous_variant	4/5		NP_001019399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARF1	ENST00000272102.10 linkuse as main transcript	c.300G>A	p.Val100=	synonymous_variant	4/5	1	NM_001658.4	ENSP00000272102	P1

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

365

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00847

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000640

AC:

161

AN:

251382

Hom.:

AF XY:

0.000515

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00880

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000215

AC:

315

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

148

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00777

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00241

AC:

367

AN:

152298

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00849

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.00289

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARF1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 29, 2024

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

-0.61

CADD

Benign

5.4

DANN

Benign

0.87

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