dbSNP rs368865411: LAIR1:p.Gly135Ser (chr19-54360034-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002287.6(LAIR1):c.403G>A(p.Gly135Ser) 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 0.000041 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LAIR1
NM_002287.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.73

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045651674).

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.403G>A	p.Gly135Ser	missense	Exon 4 of 10	NP_002278.2	Q6GTX8-1
LAIR1	NM_001289025.3		c.400G>A	p.Gly134Ser	missense	Exon 4 of 10	NP_001275954.2	D3YTC8
LAIR1	NM_001289026.3		c.382G>A	p.Gly128Ser	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.403G>A	p.Gly135Ser	missense	Exon 4 of 10	ENSP00000375622.2	Q6GTX8-1
LAIR1	ENST00000348231.8	TSL:1	c.364+882G>A		intron	N/A	ENSP00000301193.4	Q6GTX8-2
LAIR1	ENST00000474878.5	TSL:1	c.361+882G>A		intron	N/A	ENSP00000418998.1	Q6GTX8-3

Frequencies

GnomAD3 genomes

AF:

0.0000414

AC:

AN:

120916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000891

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:

0.0000352

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

249158

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000224

AC:

AN:

402248

Hom.:

Cov.:

AF XY:

0.0000337

AC XY:

AN XY:

207504

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000148

AC:

AN:

13484

American (AMR)

AF:

0.00

AC:

AN:

17718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11822

East Asian (EAS)

AF:

0.0000388

AC:

AN:

25754

South Asian (SAS)

AF:

0.00

AC:

AN:

27206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1686

European-Non Finnish (NFE)

AF:

0.0000232

AC:

AN:

258852

Other (OTH)

AF:

0.00

AC:

AN:

22562

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000255718), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.314

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000414

AC:

AN:

120916

Hom.:

Cov.:

AF XY:

0.0000705

AC XY:

AN XY:

56762

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000891

AC:

AN:

33658

American (AMR)

AF:

0.00

AC:

AN:

11678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3068

East Asian (EAS)

AF:

0.00

AC:

AN:

3384

South Asian (SAS)

AF:

0.00

AC:

AN:

3054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000352

AC:

AN:

56764

Other (OTH)

AF:

0.00

AC:

AN:

1540

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000414643), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

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.:

ESP6500AA

AF:

0.000685

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

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

0.075

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.11

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.39

M_CAP

Benign

0.0023

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.98

PhyloP100

-1.7

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.29

REVEL

Benign

0.068

Sift

Benign

0.24

Sift4G

Benign

0.43

Polyphen

0.085

Vest4

0.11

MVP

0.081

MPC

1.9

ClinPred

0.020

GERP RS

-3.8

gMVP

0.096

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over