dbSNP rs1403626: LRIG1:p.Leu24Phe (chr3-66500338-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015541.3(LRIG1):c.70C>T(p.Leu24Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. L24V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRIG1
NM_015541.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34

Publications

20 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27394682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIG1	NM_015541.3 link	c.70C>T	p.Leu24Phe	missense_variant	Exon 1 of 19	ENST00000273261.8	NP_056356.2	Q96JA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRIG1	ENST00000273261.8 link	c.70C>T	p.Leu24Phe	missense_variant	Exon 1 of 19	1	NM_015541.3	ENSP00000273261.3	Q96JA1-1
LRIG1	ENST00000383703.3 link	c.70C>T	p.Leu24Phe	missense_variant	Exon 1 of 20	1		ENSP00000373208.3	Q96JA1-2
LRIG1	ENST00000498287.5 link	n.171+755C>T		intron_variant	Intron 1 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151324

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1345108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665892

African (AFR)

AF:

0.00

AC:

AN:

28210

American (AMR)

AF:

0.00

AC:

AN:

27416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22798

East Asian (EAS)

AF:

0.00

AC:

AN:

32018

South Asian (SAS)

AF:

0.00

AC:

AN:

74288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4848

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1062276

Other (OTH)

AF:

0.00

AC:

AN:

55568

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151324

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73868

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41252

American (AMR)

AF:

0.00

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5018

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67750

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

3163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.44

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.0

M;M

PhyloP100

1.3

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.097

Sift

Benign

0.13

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.91

P;D

Vest4

0.32

MutPred

0.39

Loss of disorder (P = 0.0508);Loss of disorder (P = 0.0508);

MVP

0.27

MPC

0.32

ClinPred

0.45

GERP RS

3.1

Varity_R

0.098

gMVP

0.46

Mutation Taster

=81/19

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over