19-54281081-T-C

Position:

• chr19-54281081-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080978.4(LILRB2):​c.-169A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 144,408 control chromosomes in the GnomAD database, including 43,848 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 0.78 (43848 hom., cov: 31)
  • Exomes 𝑓: 0.66 (51677 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRB2 NM_001080978.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.34

Genes affected

LILRB2 (HGNC:6606): (leukocyte immunoglobulin like receptor B2) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.224).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB2	NM_001080978.4	c.-169A>G		5_prime_UTR_variant	1/14	ENST00000314446.10	NP_001074447.2
LILRB2	NM_001278404.3	c.-366A>G		5_prime_UTR_variant	1/13		NP_001265333.2
LILRB2	NM_005874.5	c.-169A>G		5_prime_UTR_variant	1/14		NP_005865.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB2	ENST00000314446.10	c.-169A>G		5_prime_UTR_variant	1/14	1	NM_001080978.4	ENSP00000319960	A2
LILRB2	ENST00000391749.4	c.-169A>G		5_prime_UTR_variant	1/14	1		ENSP00000375629	P4
LILRB2	ENST00000493242.1	n.17A>G		non_coding_transcript_exon_variant	1/13	1
LILRB2	ENST00000434421.5	c.-366A>G		5_prime_UTR_variant	1/13	2		ENSP00000410117

Frequencies

GnomAD3 genomes AF: 0.778 AC: 112211 AN: 144288 Hom.: 43810 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.868

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.813

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.662 AC: 174120 AN: 262844 Hom.: 51677 Cov.: 4 AF XY: 0.669 AC XY: 98304 AN XY: 146970

Gnomad4 AFR exome AF: 0.711

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.706

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.733

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.670

Gnomad4 OTH exome AF: 0.668

GnomAD4 genome AF: 0.778 AC: 112309 AN: 144408 Hom.: 43848 Cov.: 31 AF XY: 0.770 AC XY: 54219 AN XY: 70450

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.809

Alfa AF: 0.696 Hom.: 5145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs448092; hg19: -;