Variant 3-66383252-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015541.3(LRIG1):c.2221T>C(p.Leu741=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,613,978 control chromosomes in the GnomAD database, including 285,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30398 hom., cov: 33)

Exomes 𝑓: 0.59 ( 254645 hom. )

Consequence

LRIG1
NM_015541.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.52

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 3-66383252-A-G is Benign according to our data. Variant chr3-66383252-A-G is described in ClinVar as [Benign]. Clinvar id is 403054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 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.2221T>C	p.Leu741=	synonymous_variant	15/19	ENST00000273261.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIG1	ENST00000273261.8 linkuse as main transcript	c.2221T>C	p.Leu741=	synonymous_variant	15/19	1	NM_015541.3	P1	Q96JA1-1

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95433

AN:

152018

Hom.:

30342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.809

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.620

AC:

155916

AN:

251310

Hom.:

49180

AF XY:

0.616

AC XY:

83712

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.715

Gnomad AMR exome

AF:

0.673

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.823

Gnomad SAS exome

AF:

0.650

Gnomad FIN exome

AF:

0.584

Gnomad NFE exome

AF:

0.571

Gnomad OTH exome

AF:

0.593

GnomAD4 exome

AF:

0.588

AC:

859452

AN:

1461842

Hom.:

254645

Cov.:

AF XY:

0.589

AC XY:

428158

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.713

Gnomad4 AMR exome

AF:

0.668

Gnomad4 ASJ exome

AF:

0.476

Gnomad4 EAS exome

AF:

0.792

Gnomad4 SAS exome

AF:

0.648

Gnomad4 FIN exome

AF:

0.589

Gnomad4 NFE exome

AF:

0.572

Gnomad4 OTH exome

AF:

0.594

GnomAD4 genome

AF:

0.628

AC:

95552

AN:

152136

Hom.:

30398

Cov.:

AF XY:

0.630

AC XY:

46854

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.716

Gnomad4 AMR

AF:

0.646

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.808

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.580

Gnomad4 NFE

AF:

0.574

Gnomad4 OTH

AF:

0.607

Alfa

AF:

0.581

Hom.:

49027

Bravo

AF:

0.635

Asia WGS

AF:

0.714

AC:

2482

AN:

3478

EpiCase

AF:

0.573

EpiControl

AF:

0.571

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

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.3

DANN

Benign

0.81

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