Variant 3-66394191-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015541.3(LRIG1):c.1317C>T(p.Ser439Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,593,816 control chromosomes in the GnomAD database, including 50,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7842 hom., cov: 33)

Exomes 𝑓: 0.24 ( 43073 hom. )

Consequence

LRIG1
NM_015541.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.312

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:

LRIG1 (HGNC:):

LRIG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-66394191-G-A is Benign according to our data. Variant chr3-66394191-G-A is described in ClinVar as [Benign]. Clinvar id is 403056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.312 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 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.1317C>T	p.Ser439Ser	synonymous_variant	12/19	ENST00000273261.8	NP_056356.2	Q96JA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRIG1	ENST00000273261.8 linkuse as main transcript	c.1317C>T	p.Ser439Ser	synonymous_variant	12/19	1	NM_015541.3	ENSP00000273261.3	Q96JA1-1
LRIG1	ENST00000383703.3 linkuse as main transcript	c.1389C>T	p.Ser463Ser	synonymous_variant	13/20	1		ENSP00000373208.3	Q96JA1-2
LRIG1	ENST00000495037.1 linkuse as main transcript	n.333C>T		non_coding_transcript_exon_variant	4/11	2
LRIG1	ENST00000496559.6 linkuse as main transcript	n.699C>T		non_coding_transcript_exon_variant	5/12	2

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45691

AN:

152042

Hom.:

7822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0722

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.276

GnomAD3 exomes

AF:

0.258

AC:

59760

AN:

231390

Hom.:

8621

AF XY:

0.249

AC XY:

31067

AN XY:

124748

show subpopulations

Gnomad AFR exome

AF:

0.463

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0781

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.237

AC:

341994

AN:

1441656

Hom.:

43073

Cov.:

AF XY:

0.235

AC XY:

168349

AN XY:

716058

show subpopulations

Gnomad4 AFR exome

AF:

0.462

Gnomad4 AMR exome

AF:

0.371

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.0612

Gnomad4 SAS exome

AF:

0.213

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.234

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.301

AC:

45758

AN:

152160

Hom.:

7842

Cov.:

AF XY:

0.300

AC XY:

22318

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.461

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.0722

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.263

Hom.:

3871

Bravo

AF:

0.309

Asia WGS

AF:

0.174

AC:

607

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 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 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

-0.45

CADD

Benign

1.6

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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