19-54252064-A-G

Variant names:

• chr19-54252064-A-G
• rs371759073
• NM_001081442.3:c.1619T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001081442.3(LILRB5):​c.1619T>C​(p.Met540Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: LILRB5 NM_001081442.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048719376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB5	NM_001081442.3	c.1619T>C	p.Met540Thr	missense_variant	Exon 12 of 13	ENST00000449561.3	NP_001074911.2
LILRB5	NM_001304457.3	c.1592T>C	p.Met531Thr	missense_variant	Exon 12 of 13		NP_001291386.2
LILRB5	NM_006840.5	c.1616T>C	p.Met539Thr	missense_variant	Exon 12 of 13		NP_006831.2
LILRB5	NM_001081443.3	c.1319T>C	p.Met440Thr	missense_variant	Exon 11 of 12		NP_001074912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB5	ENST00000449561.3	c.1619T>C	p.Met540Thr	missense_variant	Exon 12 of 13	1	NM_001081442.3	ENSP00000406478.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000239 AC: 6 AN: 251382 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135860

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461680 Hom.: 0 Cov.: 48 AF XY: 0.0000124 AC XY: 9 AN XY: 727156

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0000447

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74444

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000144

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1619T>C (p.M540T) alteration is located in exon 12 (coding exon 12) of the LILRB5 gene. This alteration results from a T to C substitution at nucleotide position 1619, causing the methionine (M) at amino acid position 540 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
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.68
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.067
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.087	T;D;T
Vest4		0.17
MVP		0.030
MPC		0.052
ClinPred		0.039	T
GERP RS		1.7
gMVP		0.086

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs371759073; hg19: chr19-54755927;