chr19-54636848-C-A

Variant names:

• chr19-54636848-C-A
• rs41548213
• NM_001081637.3:c.1929C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_001081637.3(LILRB1):​c.1929C>A​(p.Pro643Pro) 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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 30. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 107 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB1	NM_001081637.3	c.1929C>A	p.Pro643Pro	synonymous_variant	Exon 15 of 15	ENST00000324602.12	NP_001075106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB1	ENST00000324602.12	c.1929C>A	p.Pro643Pro	synonymous_variant	Exon 15 of 15	5	NM_001081637.3	ENSP00000315997.7

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

GnomAD2 exomes AF: 0.0377 AC: 9467 AN: 251408 AF XY: 0.0389

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 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 AC: 176 AN: 33478

Gnomad4 AMR exome AF: 0.0201 AC: 900 AN: 44710

Gnomad4 ASJ exome AF: 0.0596 AC: 1557 AN: 26116

Gnomad4 EAS exome AF: 0.000227 AC: 9 AN: 39698

Gnomad4 SAS exome AF: 0.0455 AC: 3921 AN: 86234

Gnomad4 FIN exome AF: 0.0467 AC: 2494 AN: 53418

Gnomad4 NFE exome AF: 0.0494 AC: 54883 AN: 1111672

Gnomad4 Remaining exome AF: 0.0427 AC: 2579 AN: 60376

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 AC: 0.00833293 AN: 0.00833293

Gnomad4 AMR AF: 0.0227 AC: 0.0226797 AN: 0.0226797

Gnomad4 ASJ AF: 0.0590 AC: 0.0590438 AN: 0.0590438

Gnomad4 EAS AF: 0.00117 AC: 0.00116505 AN: 0.00116505

Gnomad4 SAS AF: 0.0413 AC: 0.0412692 AN: 0.0412692

Gnomad4 FIN AF: 0.0380 AC: 0.0379974 AN: 0.0379974

Gnomad4 NFE AF: 0.0502 AC: 0.0501515 AN: 0.0501515

Gnomad4 OTH AF: 0.0370 AC: 0.0369668 AN: 0.0369668

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
Mutation Taster		=100/0	polymorphism (auto)

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;