rs41548213

chr19-54636848-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_001081637.3(LILRB1):c.1929C>A(p.Pro643=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 1,613,652 control chromosomes in the GnomAD database, including 1,763 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.033 (107 hom., cov: 30)
  • Exomes 𝑓: 0.046 (1656 hom.)
• Consequence: LILRB1 NM_001081637.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829

Genes affected

LILRB1 (HGNC:6605): (leukocyte immunoglobulin like receptor B1) 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). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

LILRB1-AS1 (HGNC:53114): (LILRB1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=0.829 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.033 (5022/152182) while in subpopulation NFE AF= 0.0502 (3410/67994). AF 95% confidence interval is 0.0487. There are 107 homozygotes in gnomad4. There are 2327 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 108 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LILRB1	NM_001081637.3	c.1929C>A	p.Pro643=	synonymous_variant	15/15	ENST00000324602.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LILRB1	ENST00000324602.12	c.1929C>A	p.Pro643=	synonymous_variant	15/15	5	NM_001081637.3	P4
LILRB1-AS1	ENST00000456337.1	n.200-772G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5023 AN: 152064 Hom.: 108 Cov.: 30

Gnomad AFR AF: 0.00836

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0378

GnomAD3 exomes AF: 0.0377 AC: 9467 AN: 251408 Hom.: 226 AF XY: 0.0389 AC XY: 5285 AN XY: 135880

Gnomad AFR exome AF: 0.00707

Gnomad AMR exome AF: 0.0200

Gnomad ASJ exome AF: 0.0575

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0442

Gnomad FIN exome AF: 0.0430

Gnomad NFE exome AF: 0.0484

Gnomad OTH exome AF: 0.0463

GnomAD4 exome AF: 0.0456 AC: 66642 AN: 1461470 Hom.: 1656 Cov.: 37 AF XY: 0.0458 AC XY: 33269 AN XY: 727054

Gnomad4 AFR exome AF: 0.00526

Gnomad4 AMR exome AF: 0.0201

Gnomad4 ASJ exome AF: 0.0596

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0455

Gnomad4 FIN exome AF: 0.0467

Gnomad4 NFE exome AF: 0.0494

Gnomad4 OTH exome AF: 0.0427

GnomAD4 genome AF: 0.0330 AC: 5022 AN: 152182 Hom.: 107 Cov.: 30 AF XY: 0.0313 AC XY: 2327 AN XY: 74390

Gnomad4 AFR AF: 0.00833

Gnomad4 AMR AF: 0.0227

Gnomad4 ASJ AF: 0.0590

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.0413

Gnomad4 FIN AF: 0.0380

Gnomad4 NFE AF: 0.0502

Gnomad4 OTH AF: 0.0370

Alfa AF: 0.0442 Hom.: 65

Bravo AF: 0.0311

Asia WGS AF: 0.0220 AC: 75 AN: 3478

EpiCase AF: 0.0481

EpiControl AF: 0.0413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.8
Dann	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs41548213; hg19: chr19-55148299;