rs763391018

Variant names:

• chr19-54360981-C-G
• rs763391018
• NM_002287.6:c.299G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-54360981-C-G
• chr19-54360981-C-T
• chr19-54360981-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002287.6(LAIR1):​c.299G>C​(p.Arg100Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R100H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: LAIR1 NM_002287.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -9.99
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26574415).

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.299G>C	p.Arg100Pro	missense	Exon 3 of 10	NP_002278.2	Q6GTX8-1
	LAIR1	NM_001289025.3		c.296G>C	p.Arg99Pro	missense	Exon 3 of 10	NP_001275954.2	D3YTC8
	LAIR1	NM_001289026.3		c.278G>C	p.Arg93Pro	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.299G>C	p.Arg100Pro	missense	Exon 3 of 10	ENSP00000375622.2	Q6GTX8-1
	LAIR1	ENST00000348231.8	TSL:1	c.299G>C	p.Arg100Pro	missense	Exon 3 of 9	ENSP00000301193.4	Q6GTX8-2
	LAIR1	ENST00000474878.5	TSL:1	c.296G>C	p.Arg99Pro	missense	Exon 3 of 9	ENSP00000418998.1	Q6GTX8-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251488 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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727240

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

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: 0.00 AC: 0 AN: 86256

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: 0.00000360 AC: 4 AN: 1111990

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0010
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.75	T
PhyloP100		-10
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.14
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.61		Gain of disorder (P = 0.0761)
MVP		0.21
MPC		0.34
ClinPred		0.53	D
GERP RS		-6.0
PromoterAI		-0.050	Neutral
gMVP		0.68
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs763391018; hg19: chr19-54872588;