Genetic Variant LRIG1:p.Leu26Ile (chr3-66500332-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015541.3(LRIG1):c.76C>A(p.Leu26Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,343,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L26V) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

LRIG1
NM_015541.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

21 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16857654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015541.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRIG1	NM_015541.3	MANE Select	c.76C>A	p.Leu26Ile	missense	Exon 1 of 19	NP_056356.2	Q96JA1-1
LRIG1	NM_001377344.1		c.76C>A	p.Leu26Ile	missense	Exon 1 of 18	NP_001364273.1
LRIG1	NM_001377345.1		c.-563+761C>A		intron	N/A	NP_001364274.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRIG1	ENST00000273261.8	TSL:1 MANE Select	c.76C>A	p.Leu26Ile	missense	Exon 1 of 19	ENSP00000273261.3	Q96JA1-1
LRIG1	ENST00000383703.3	TSL:1	c.76C>A	p.Leu26Ile	missense	Exon 1 of 20	ENSP00000373208.3	Q96JA1-2
LRIG1	ENST00000895940.1		c.76C>A	p.Leu26Ile	missense	Exon 1 of 20	ENSP00000565999.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

114698

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1343772

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

665088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28212

American (AMR)

AF:

0.00

AC:

AN:

27316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22816

East Asian (EAS)

AF:

0.00

AC:

AN:

31984

South Asian (SAS)

AF:

0.00

AC:

AN:

74208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4758

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1061668

Other (OTH)

AF:

0.00

AC:

AN:

55520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

3308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.094

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.59

M_CAP

Benign

0.076

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.3

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.51

REVEL

Benign

0.088

Sift

Benign

0.12

Sift4G

Benign

0.067

Polyphen

0.32

Vest4

0.28

MutPred

0.45

Loss of disorder (P = 0.0433)

MVP

0.25

MPC

0.23

ClinPred

0.24

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.34

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over