1-230979169-A-T

Position:

chr1-230979169-A-T

Variant summary

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

The NM_022786.3(ARV1):c.64A>T(p.Thr22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,611,858 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 7 hom. )

Consequence

ARV1
NM_022786.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.159

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004591197).

BP6

Variant 1-230979169-A-T is Benign according to our data. Variant chr1-230979169-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 777986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-230979169-A-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00193 (293/151628) while in subpopulation SAS AF= 0.00376 (18/4792). AF 95% confidence interval is 0.00246. There are 1 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARV1	NM_022786.3 linkuse as main transcript	c.64A>T	p.Thr22Ser	missense_variant	1/6	ENST00000310256.7	NP_073623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARV1	ENST00000310256.7 linkuse as main transcript	c.64A>T	p.Thr22Ser	missense_variant	1/6	1	NM_022786.3	ENSP00000312458	P1

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

294

AN:

151510

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000461

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00375

Gnomad FIN

AF:

0.00398

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00280

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00203

AC:

506

AN:

249286

Hom.:

AF XY:

0.00228

AC XY:

307

AN XY:

134830

show subpopulations

Gnomad AFR exome

AF:

0.000497

Gnomad AMR exome

AF:

0.000996

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00289

Gnomad FIN exome

AF:

0.00323

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00282

AC:

4116

AN:

1460230

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

1997

AN XY:

726378

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.000942

Gnomad4 ASJ exome

AF:

0.000384

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00322

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.00305

Gnomad4 OTH exome

AF:

0.00327

GnomAD4 genome

AF:

0.00193

AC:

293

AN:

151628

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

149

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.000460

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00376

Gnomad4 FIN

AF:

0.00398

Gnomad4 NFE

AF:

0.00279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00163

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00182

AC:

221

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00262

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ARV1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 12, 2020

- -

ARV1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2020

This variant is classified as likely 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

Benign

0.079

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.5

DANN

Benign

0.81

DEOGEN2

Benign

0.096

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.0070

Sift

Benign

0.28

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0010

B;.

Vest4

0.20

MutPred

0.14

Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);

MVP

0.37

MPC

0.15

ClinPred

0.0016

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.040

gMVP

0.30

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