Genetic Variant LAIR1:p.Ser129Cys (chr19-54360051-G-C) – 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.386C>G(p.Ser129Cys) 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. 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. S129F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 15)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LAIR1
NM_002287.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0240

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=0.10060683).

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.386C>G	p.Ser129Cys	missense	Exon 4 of 10	NP_002278.2	Q6GTX8-1
LAIR1	NM_001289025.3		c.383C>G	p.Ser128Cys	missense	Exon 4 of 10	NP_001275954.2	D3YTC8
LAIR1	NM_001289026.3		c.365C>G	p.Ser122Cys	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.386C>G	p.Ser129Cys	missense	Exon 4 of 10	ENSP00000375622.2	Q6GTX8-1
LAIR1	ENST00000348231.8	TSL:1	c.364+865C>G		intron	N/A	ENSP00000301193.4	Q6GTX8-2
LAIR1	ENST00000474878.5	TSL:1	c.361+865C>G		intron	N/A	ENSP00000418998.1	Q6GTX8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

250222

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

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

AF:

0.00

AC:

AN:

423528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

218052

African (AFR)

AF:

0.00

AC:

AN:

13880

American (AMR)

AF:

0.00

AC:

AN:

17910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12090

East Asian (EAS)

AF:

0.00

AC:

AN:

26182

South Asian (SAS)

AF:

0.00

AC:

AN:

29156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1774

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

275588

Other (OTH)

AF:

0.00

AC:

AN:

23306

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.12

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.55

M_CAP

Benign

0.0033

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.93

PhyloP100

0.024

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

REVEL

Benign

0.021

Sift

Uncertain

0.011

Sift4G

Uncertain

0.045

Polyphen

0.99

Vest4

0.17

MutPred

0.19

Loss of phosphorylation at S129 (P = 0.0096)

MVP

0.27

MPC

2.0

ClinPred

0.099

GERP RS

0.80

gMVP

0.14

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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