Genetic Variant LAIR1:p.Asp128Tyr (chr19-54360055-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002287.6(LAIR1):c.382G>T(p.Asp128Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 15)

Failed GnomAD Quality Control

Consequence

LAIR1
NM_002287.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.350

Variant links:

Genes affected

LAIR1 (HGNC:6477): (leukocyte associated immunoglobulin like receptor 1) The protein encoded by this gene is an inhibitory receptor found on peripheral mononuclear cells, including natural killer cells, T cells, and B cells. Inhibitory receptors regulate the immune response to prevent lysis of cells recognized as self. The gene is a member of both the immunoglobulin superfamily and the leukocyte-associated inhibitory receptor family. The gene maps to a region of 19q13.4 called the leukocyte receptor cluster, which contains at least 29 genes encoding leukocyte-expressed receptors of the immunoglobulin superfamily. The encoded protein has been identified as an anchor for tyrosine phosphatase SHP-1, and may induce cell death in myeloid leukemias. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

LAIR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10247719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAIR1	NM_002287.6 link	c.382G>T	p.Asp128Tyr	missense_variant	Exon 4 of 10	ENST00000391742.7	NP_002278.2	Q6GTX8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAIR1	ENST00000391742.7 link	c.382G>T	p.Asp128Tyr	missense_variant	Exon 4 of 10	1	NM_002287.6	ENSP00000375622.2		Q6GTX8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

117986

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

117986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

55084

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.382G>T (p.D128Y) alteration is located in exon 4 (coding exon 4) of the LAIR1 gene. This alteration results from a G to T substitution at nucleotide position 382, causing the aspartic acid (D) at amino acid position 128 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.015

.;T;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.61

.;T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.46

N;N;N;.

REVEL

Benign

0.052

Sift

Benign

0.053

T;T;T;.

Sift4G

Benign

0.074

T;T;T;D

Polyphen

0.94, 0.50

.;P;P;.

Vest4

0.18

MutPred

0.19

Gain of phosphorylation at D128 (P = 0.0238);.;.;.;

MVP

0.40

MPC

2.3

ClinPred

0.15

GERP RS

-1.0

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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