rs448092

Variant names:

• chr19-54281081-T-C
• rs448092
• NM_001080978.4:c.-169A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080978.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB2	NM_001080978.4	MANE Select	c.-169A>G		5_prime_UTR	Exon 1 of 14	NP_001074447.2
	LILRB2	NM_005874.5		c.-169A>G		5_prime_UTR	Exon 1 of 14	NP_005865.3
	LILRB2	NM_001278404.3		c.-366A>G		5_prime_UTR	Exon 1 of 13	NP_001265333.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB2	ENST00000314446.10	TSL:1 MANE Select	c.-169A>G		5_prime_UTR	Exon 1 of 14	ENSP00000319960.5
	LILRB2	ENST00000391749.4	TSL:1	c.-169A>G		5_prime_UTR	Exon 1 of 14	ENSP00000375629.4
	LILRB2	ENST00000493242.1	TSL:1	n.17A>G		non_coding_transcript_exon	Exon 1 of 13

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

African (AFR) AF: 0.711 AC: 5242 AN: 7368

American (AMR) AF: 0.562 AC: 12650 AN: 22514

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 5643 AN: 7990

East Asian (EAS) AF: 0.335 AC: 2965 AN: 8860

South Asian (SAS) AF: 0.733 AC: 38665 AN: 52738

European-Finnish (FIN) AF: 0.610 AC: 6806 AN: 11162

Middle Eastern (MID) AF: 0.741 AC: 1275 AN: 1720

European-Non Finnish (NFE) AF: 0.670 AC: 92816 AN: 138436

Other (OTH) AF: 0.668 AC: 8058 AN: 12056

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

African (AFR) AF: 0.823 AC: 31909 AN: 38772

American (AMR) AF: 0.752 AC: 10943 AN: 14550

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 2947 AN: 3310

East Asian (EAS) AF: 0.357 AC: 1820 AN: 5098

South Asian (SAS) AF: 0.789 AC: 3559 AN: 4512

European-Finnish (FIN) AF: 0.685 AC: 6880 AN: 10050

Middle Eastern (MID) AF: 0.869 AC: 245 AN: 282

European-Non Finnish (NFE) AF: 0.795 AC: 51652 AN: 64996

Other (OTH) AF: 0.809 AC: 1593 AN: 1970

Alfa AF: 0.696 Hom.: 5145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.22
PhyloP100		-4.3
PromoterAI		-0.0073	Neutral

Splicing

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

Other links and lift over

dbSNP: rs448092;