19-54355344-G-A

Position:

• chr19-54355344-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002287.6(LAIR1):​c.788C>T​(p.Thr263Ile) 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 benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LAIR1 NM_002287.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11583719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAIR1	NM_002287.6	c.788C>T	p.Thr263Ile	missense_variant	10/10	ENST00000391742.7	NP_002278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAIR1	ENST00000391742.7	c.788C>T	p.Thr263Ile	missense_variant	10/10	1	NM_002287.6	ENSP00000375622.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.788C>T (p.T263I) alteration is located in exon 10 (coding exon 10) of the LAIR1 gene. This alteration results from a C to T substitution at nucleotide position 788, causing the threonine (T) at amino acid position 263 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	.;T;.;.;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.73	.;T;.;T;.
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.1	N;N;N;N;N
REVEL	Benign	0.053
Sift	Uncertain	0.014	D;D;D;D;D
Sift4G	Benign	0.25	T;T;T;T;T
Polyphen		0.99, 0.82	.;D;.;P;.
Vest4		0.059
MutPred		0.42		Loss of sheet (P = 0.0037);.;.;.;.;
MVP		0.27
MPC		0.85
ClinPred		0.61	D
GERP RS		1.4
gMVP		0.15

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54866953;