chr19-54594932-C-T

Position:

• chr19-54594932-C-T

Variant summary

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

The ENST00000251372.8(LILRA1):​c.338C>T​(p.Pro113Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LILRA1 ENST00000251372.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.769

Genes affected

LILRA1 (HGNC:6602): (leukocyte immunoglobulin like receptor A1) This gene encodes an activating member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein is predominantly expressed in B cells, interacts with major histocompatibility complex class I ligands, and contributes to the regulation of immune responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

LILRA1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA1	NM_006863.4	c.338C>T	p.Pro113Leu	missense_variant	4/10	ENST00000251372.8	NP_006854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA1	ENST00000251372.8	c.338C>T	p.Pro113Leu	missense_variant	4/10	1	NM_006863.4	ENSP00000251372.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 33

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

Feb 13, 2024

The c.338C>T (p.P113L) alteration is located in exon 4 (coding exon 3) of the LILRA1 gene. This alteration results from a C to T substitution at nucleotide position 338, causing the proline (P) at amino acid position 113 to be replaced by a leucine (L). 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
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0070	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.057	N
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M;M
MutationTaster	Benign	0.95	N;N;D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-8.3	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.99	D;D
Vest4		0.21
MutPred		0.52		Loss of disorder (P = 0.0384);Loss of disorder (P = 0.0384);
MVP		0.46
MPC		0.13
ClinPred		0.90	D
GERP RS		0.51
Varity_R		0.17
gMVP		0.053

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: chr19-55106397;