Variant 3-66380446-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_015541.3(LRIG1):c.3099C>T(p.Ser1033=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 1,614,124 control chromosomes in the GnomAD database, including 3,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.049 ( 230 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3423 hom. )

Consequence

LRIG1
NM_015541.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.05

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-66380446-G-A is Benign according to our data. Variant chr3-66380446-G-A is described in ClinVar as [Benign]. Clinvar id is 3038396.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0746 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.3099C>T	p.Ser1033=	synonymous_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.3099C>T	p.Ser1033=	synonymous_variant	19/19	1	NM_015541.3	P1	Q96JA1-1

Frequencies

GnomAD3 genomes

AF:

0.0487

AC:

7408

AN:

152142

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.0210

Gnomad SAS

AF:

0.0812

Gnomad FIN

AF:

0.0555

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0699

Gnomad OTH

AF:

0.0468

GnomAD3 exomes

AF:

0.0579

AC:

14458

AN:

249578

Hom.:

506

AF XY:

0.0613

AC XY:

8278

AN XY:

134972

show subpopulations

Gnomad AFR exome

AF:

0.0122

Gnomad AMR exome

AF:

0.0445

Gnomad ASJ exome

AF:

0.0464

Gnomad EAS exome

AF:

0.0182

Gnomad SAS exome

AF:

0.0784

Gnomad FIN exome

AF:

0.0500

Gnomad NFE exome

AF:

0.0719

Gnomad OTH exome

AF:

0.0640

GnomAD4 exome

AF:

0.0663

AC:

96954

AN:

1461864

Hom.:

3423

Cov.:

AF XY:

0.0669

AC XY:

48637

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0119

Gnomad4 AMR exome

AF:

0.0450

Gnomad4 ASJ exome

AF:

0.0440

Gnomad4 EAS exome

AF:

0.0346

Gnomad4 SAS exome

AF:

0.0786

Gnomad4 FIN exome

AF:

0.0508

Gnomad4 NFE exome

AF:

0.0708

Gnomad4 OTH exome

AF:

0.0592

GnomAD4 genome

AF:

0.0486

AC:

7405

AN:

152260

Hom.:

230

Cov.:

AF XY:

0.0487

AC XY:

3628

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.0436

Gnomad4 ASJ

AF:

0.0447

Gnomad4 EAS

AF:

0.0206

Gnomad4 SAS

AF:

0.0813

Gnomad4 FIN

AF:

0.0555

Gnomad4 NFE

AF:

0.0699

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0621

Hom.:

182

Bravo

AF:

0.0450

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.0665

EpiControl

AF:

0.0697

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

Feb 19, 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

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.42

DANN

Benign

0.54

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