rs2306272

Positions:

chr3-66384219-T-C

Variant summary

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

The NM_015541.3(LRIG1):c.1843A>G(p.Met615Val) variant causes a missense change. The variant allele was found at a frequency of 0.294 in 1,613,766 control chromosomes in the GnomAD database, including 76,066 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.26 ( 6217 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69849 hom. )

Consequence

LRIG1
NM_015541.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.21

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:

LRIG1 (HGNC:):

LRIG1 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=4.7625545E-6).

BP6

Variant 3-66384219-T-C is Benign according to our data. Variant chr3-66384219-T-C is described in ClinVar as [Benign]. Clinvar id is 403055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIG1	NM_015541.3 linkuse as main transcript	c.1843A>G	p.Met615Val	missense_variant	14/19	ENST00000273261.8	NP_056356.2	Q96JA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIG1	ENST00000273261.8 linkuse as main transcript	c.1843A>G	p.Met615Val	missense_variant	14/19	1	NM_015541.3	ENSP00000273261.3		Q96JA1-1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39764

AN:

151900

Hom.:

6205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.729

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.279

GnomAD3 exomes

AF:

0.312

AC:

78294

AN:

250908

Hom.:

14547

AF XY:

0.317

AC XY:

43049

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.746

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.298

AC:

434876

AN:

1461748

Hom.:

69849

Cov.:

AF XY:

0.300

AC XY:

218406

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.253

Gnomad4 EAS exome

AF:

0.714

Gnomad4 SAS exome

AF:

0.371

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.262

AC:

39789

AN:

152018

Hom.:

6217

Cov.:

AF XY:

0.265

AC XY:

19707

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.728

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.250

Gnomad4 NFE

AF:

0.283

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.284

Hom.:

14500

Bravo

AF:

0.260

TwinsUK

AF:

0.283

AC:

1050

ALSPAC

AF:

0.286

AC:

1102

ESP6500AA

AF:

0.145

AC:

637

ESP6500EA

AF:

0.274

AC:

2358

ExAC

AF:

0.313

AC:

38028

Asia WGS

AF:

0.502

AC:

1743

AN:

3478

EpiCase

AF:

0.288

EpiControl

AF:

0.285

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

LRIG1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 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). -

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.057

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.0000048

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.33

N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.069

Sift

Benign

0.37

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0070

B;B

Vest4

0.092

MPC

0.13

ClinPred

0.014

GERP RS

5.0

Varity_R

0.26

gMVP

0.36

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