NM_002287.6:c.289G>T

Variant names:

• chr19-54360991-C-A
• rs1425720525
• NM_002287.6:c.289G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002287.6(LAIR1):​c.289G>T​(p.Gly97Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G97R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LAIR1 NM_002287.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAIR1	NM_002287.6	MANE Select	c.289G>T	p.Gly97Trp	missense	Exon 3 of 10	NP_002278.2	Q6GTX8-1
	LAIR1	NM_001289025.3		c.286G>T	p.Gly96Trp	missense	Exon 3 of 10	NP_001275954.2	D3YTC8
	LAIR1	NM_001289026.3		c.268G>T	p.Gly90Trp	missense	Exon 3 of 10	NP_001275955.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAIR1	ENST00000391742.7	TSL:1 MANE Select	c.289G>T	p.Gly97Trp	missense	Exon 3 of 10	ENSP00000375622.2	Q6GTX8-1
	LAIR1	ENST00000348231.8	TSL:1	c.289G>T	p.Gly97Trp	missense	Exon 3 of 9	ENSP00000301193.4	Q6GTX8-2
	LAIR1	ENST00000474878.5	TSL:1	c.286G>T	p.Gly96Trp	missense	Exon 3 of 9	ENSP00000418998.1	Q6GTX8-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251494 AF XY: 0.00000736

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: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 62 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.99	T
PhyloP100		-0.082
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.81		Loss of disorder (P = 0.0172)
MVP		0.44
MPC		0.33
ClinPred		1.0	D
GERP RS		1.9
PromoterAI		0.011	Neutral
gMVP		0.62
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1425720525; hg19: chr19-54872598;