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

Variant summary

Our verdict is Likely benign. The variant received -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. 15/20 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

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002287.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAIR1	NM_002287.6	MANE Select	c.382G>T	p.Asp128Tyr	missense	Exon 4 of 10	NP_002278.2	Q6GTX8-1
LAIR1	NM_001289025.3		c.379G>T	p.Asp127Tyr	missense	Exon 4 of 10	NP_001275954.2	D3YTC8
LAIR1	NM_001289026.3		c.361G>T	p.Asp121Tyr	missense	Exon 4 of 10	NP_001275955.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAIR1	ENST00000391742.7	TSL:1 MANE Select	c.382G>T	p.Asp128Tyr	missense	Exon 4 of 10	ENSP00000375622.2	Q6GTX8-1
LAIR1	ENST00000348231.8	TSL:1	c.364+861G>T		intron	N/A	ENSP00000301193.4	Q6GTX8-2
LAIR1	ENST00000474878.5	TSL:1	c.361+861G>T		intron	N/A	ENSP00000418998.1	Q6GTX8-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

117986

Hom.:

Cov.:

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

African (AFR)

AF:

0.00

AC:

AN:

32786

American (AMR)

AF:

0.00

AC:

AN:

11266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3034

East Asian (EAS)

AF:

0.00

AC:

AN:

3310

South Asian (SAS)

AF:

0.00

AC:

AN:

2918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

55664

Other (OTH)

AF:

0.00

AC:

AN:

1536

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.015

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.61

M_CAP

Benign

0.0019

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

PhyloP100

-0.35

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.46

REVEL

Benign

0.052

Sift

Benign

0.053

Sift4G

Benign

0.074

Polyphen

0.94

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

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over