Variant 1-230990117-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_022786.3(ARV1):c.302G>A(p.Gly101Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,603,664 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 63 hom. )

Consequence

ARV1
NM_022786.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.58

Variant links:

Genes affected

ARV1 (HGNC:29561): (ARV1 homolog, fatty acid homeostasis modulator) this gene encodes a transmembrane protein that contains a conserved zinc ribbon motif at the N- terminus. A similar protein in mouse is thought to function in fatty acid homeostasis. Mutations in this gene are associated with early infantile epileptic encephalopathy 38. [provided by RefSeq, Nov 2016]

ARV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-230990117-G-A is Benign according to our data. Variant chr1-230990117-G-A is described in ClinVar as [Benign]. Clinvar id is 789436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00412 (627/152326) while in subpopulation SAS AF= 0.0195 (94/4828). AF 95% confidence interval is 0.0163. There are 4 homozygotes in gnomad4. There are 294 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARV1	NM_022786.3 linkuse as main transcript	c.302G>A	p.Gly101Glu	missense_variant	3/6	ENST00000310256.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARV1	ENST00000310256.7 linkuse as main transcript	c.302G>A	p.Gly101Glu	missense_variant	3/6	1	NM_022786.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00414

AC:

630

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00607

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00565

AC:

1359

AN:

240508

Hom.:

AF XY:

0.00677

AC XY:

881

AN XY:

130210

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00175

Gnomad ASJ exome

AF:

0.00513

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.0207

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00557

Gnomad OTH exome

AF:

0.00616

GnomAD4 exome

AF:

0.00682

AC:

9903

AN:

1451338

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

5202

AN XY:

721824

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00196

Gnomad4 ASJ exome

AF:

0.00498

Gnomad4 EAS exome

AF:

0.0000762

Gnomad4 SAS exome

AF:

0.0203

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00661

Gnomad4 OTH exome

AF:

0.00887

GnomAD4 genome

AF:

0.00412

AC:

627

AN:

152326

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00607

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00569

Hom.:

Bravo

AF:

0.00422

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00562

AC:

683

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.00705

EpiControl

AF:

0.00593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ARV1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2019

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

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.26

Sift

Benign

0.38

T;T

Sift4G

Benign

0.82

T;T

Polyphen

1.0

D;.

Vest4

0.84

MVP

0.90

MPC

0.78

ClinPred

0.017

GERP RS

6.2

Varity_R

0.60

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.30

Position offset: 33

DS_AL_spliceai

0.21

Position offset: -7

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