19-54254403-T-G

Variant names:

• chr19-54254403-T-G
• rs2079053180
• NM_001081442.3:c.1268A>C

Variant summary

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

The NM_001081442.3(LILRB5):​c.1268A>C​(p.Asp423Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LILRB5 NM_001081442.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.63

Genes affected

LILRB5 (HGNC:6609): (leukocyte immunoglobulin like receptor B5) This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Several other LIR subfamily B receptors are expressed on immune cells where they bind to MHC class I molecules on antigen-presenting cells and inhibit stimulation of an immune response. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.06809333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB5	NM_001081442.3	c.1268A>C	p.Asp423Ala	missense_variant	Exon 7 of 13	ENST00000449561.3	NP_001074911.2
LILRB5	NM_001304457.3	c.1241A>C	p.Asp414Ala	missense_variant	Exon 7 of 13		NP_001291386.2
LILRB5	NM_006840.5	c.1268A>C	p.Asp423Ala	missense_variant	Exon 7 of 13		NP_006831.2
LILRB5	NM_001081443.3	c.968A>C	p.Asp323Ala	missense_variant	Exon 6 of 12		NP_001074912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB5	ENST00000449561.3	c.1268A>C	p.Asp423Ala	missense_variant	Exon 7 of 13	1	NM_001081442.3	ENSP00000406478.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433318 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 710026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1268A>C (p.D423A) alteration is located in exon 7 (coding exon 7) of the LILRB5 gene. This alteration results from a A to C substitution at nucleotide position 1268, causing the aspartic acid (D) at amino acid position 423 to be replaced by an alanine (A). 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	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.13
DANN	Benign	0.42
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0029	N
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.068	T;T;T
MetaSVM	Benign	-0.89	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.63	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.38	T;T;T
Sift4G	Benign	0.35	T;T;T
Vest4		0.059
MVP		0.10
MPC		0.059
ClinPred		0.045	T
GERP RS		-3.9
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs2079053180; hg19: chr19-54758266;