19-54356233-C-T

Variant names:

• chr19-54356233-C-T
• NM_002287.6:c.661G>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.661G>A​(p.Ala221Thr) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LAIR1 NM_002287.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.235

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=0.07415035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAIR1	NM_002287.6	c.661G>A	p.Ala221Thr	missense_variant	Exon 8 of 10	ENST00000391742.7	NP_002278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAIR1	ENST00000391742.7	c.661G>A	p.Ala221Thr	missense_variant	Exon 8 of 10	1	NM_002287.6	ENSP00000375622.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.661G>A (p.A221T) alteration is located in exon 8 (coding exon 8) of the LAIR1 gene. This alteration results from a G to A substitution at nucleotide position 661, causing the alanine (A) at amino acid position 221 to be replaced by a threonine (T). 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	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0089	.;T;.;.;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.74	.;T;.;T;.
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.074	T;T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.77	N;N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.081	T;T;D;T;D
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.16, 0.089	.;B;.;B;.
Vest4		0.048
MutPred		0.26		Loss of sheet (P = 3e-04);.;.;.;.;
MVP		0.18
MPC		0.27
ClinPred		0.090	T
GERP RS		0.28
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54867842;