Variant chr3-66380763-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015541.3(LRIG1):c.2869G>A(p.Ala957Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 1,614,116 control chromosomes in the GnomAD database, including 2,594 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.080 ( 682 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1912 hom. )

Consequence

LRIG1
NM_015541.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.37

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.95487E-4).

BP6

Variant 3-66380763-C-T is Benign according to our data. Variant chr3-66380763-C-T is described in ClinVar as [Benign]. Clinvar id is 3055912.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 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.2869G>A	p.Ala957Thr	missense_variant	18/19	ENST00000273261.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIG1	ENST00000273261.8 linkuse as main transcript	c.2869G>A	p.Ala957Thr	missense_variant	18/19	1	NM_015541.3	P1	Q96JA1-1

Frequencies

GnomAD3 genomes

AF:

0.0795

AC:

12093

AN:

152130

Hom.:

683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0707

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0933

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0434

Gnomad OTH

AF:

0.0774

GnomAD3 exomes

AF:

0.0536

AC:

13479

AN:

251386

Hom.:

569

AF XY:

0.0487

AC XY:

6624

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.0726

Gnomad ASJ exome

AF:

0.0386

Gnomad EAS exome

AF:

0.0115

Gnomad SAS exome

AF:

0.0154

Gnomad FIN exome

AF:

0.0933

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0570

GnomAD4 exome

AF:

0.0427

AC:

62459

AN:

1461868

Hom.:

1912

Cov.:

AF XY:

0.0418

AC XY:

30374

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.0731

Gnomad4 ASJ exome

AF:

0.0378

Gnomad4 EAS exome

AF:

0.0182

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0895

Gnomad4 NFE exome

AF:

0.0384

Gnomad4 OTH exome

AF:

0.0467

GnomAD4 genome

AF:

0.0795

AC:

12104

AN:

152248

Hom.:

682

Cov.:

AF XY:

0.0805

AC XY:

5993

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0705

Gnomad4 ASJ

AF:

0.0389

Gnomad4 EAS

AF:

0.0130

Gnomad4 SAS

AF:

0.0199

Gnomad4 FIN

AF:

0.0933

Gnomad4 NFE

AF:

0.0434

Gnomad4 OTH

AF:

0.0780

Alfa

AF:

0.0466

Hom.:

554

Bravo

AF:

0.0821

TwinsUK

AF:

0.0391

AC:

145

ALSPAC

AF:

0.0348

AC:

134

ESP6500AA

AF:

0.160

AC:

706

ESP6500EA

AF:

0.0423

AC:

364

ExAC

AF:

0.0548

AC:

6654

Asia WGS

AF:

0.0450

AC:

158

AN:

3478

EpiCase

AF:

0.0357

EpiControl

AF:

0.0381

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LRIG1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 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

0.089

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0030

DANN

Benign

0.68

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.039

MetaRNN

Benign

0.0010

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.77

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.13

Sift

Benign

0.70

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0

B;B

Vest4

0.017

MPC

0.089

ClinPred

0.0031

GERP RS

-12

Varity_R

0.013

gMVP

0.0087

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