chr3-66380387-T-G

Position:

chr3-66380387-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015541.3(LRIG1):c.3158A>C(p.Gln1053Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,614,060 control chromosomes in the GnomAD database, including 29,674 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 0.16 ( 2216 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27458 hom. )

Consequence

LRIG1
NM_015541.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

LRIG1 (HGNC:17360): (leucine rich repeats and immunoglobulin like domains 1) Predicted to act upstream of or within several processes, including innervation; otolith morphogenesis; and sensory perception of sound. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LRIG1 links:

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

SLC25A26 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=9.765923E-4).

BP6

Variant 3-66380387-T-G is Benign according to our data. Variant chr3-66380387-T-G is described in ClinVar as [Benign]. Clinvar id is 403053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRIG1	NM_015541.3 linkuse as main transcript	c.3158A>C	p.Gln1053Pro	missense_variant	19/19	ENST00000273261.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIG1	ENST00000273261.8 linkuse as main transcript	c.3158A>C	p.Gln1053Pro	missense_variant	19/19	1	NM_015541.3	P1	Q96JA1-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24171

AN:

152088

Hom.:

2217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0950

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.0617

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.160

AC:

40208

AN:

251116

Hom.:

3651

AF XY:

0.162

AC XY:

22047

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.0870

Gnomad AMR exome

AF:

0.0910

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.0656

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.189

AC:

275573

AN:

1461854

Hom.:

27458

Cov.:

AF XY:

0.187

AC XY:

135884

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0926

Gnomad4 AMR exome

AF:

0.0968

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.0541

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.159

AC:

24168

AN:

152206

Hom.:

2216

Cov.:

AF XY:

0.157

AC XY:

11658

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0949

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.0615

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.183

Hom.:

5205

Bravo

AF:

0.146

TwinsUK

AF:

0.206

AC:

765

ALSPAC

AF:

0.210

AC:

809

ESP6500AA

AF:

0.0967

AC:

426

ESP6500EA

AF:

0.201

AC:

1726

ExAC

AF:

0.162

AC:

19671

Asia WGS

AF:

0.110

AC:

383

AN:

3478

EpiCase

AF:

0.200

EpiControl

AF:

0.201

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

LRIG1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

Benign

0.093

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.86

MetaRNN

Benign

0.00098

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

M;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.010

D;D

Sift4G

Benign

0.15

T;T

Polyphen

0.23

B;P

Vest4

0.50

MPC

0.14

ClinPred

0.022

GERP RS

3.1

Varity_R

0.16

gMVP

0.37

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