rs41308748

Variant names:

• chr19-54636725-G-A
• rs41308748
• NM_001081637.3:c.1813-7G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54636725-G-A
• chr19-54636725-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001081637.3(LILRB1):​c.1813-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,191,938 control chromosomes in the GnomAD database, including 1,572 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.070 (99 hom., cov: 17)
  • Exomes 𝑓: 0.061 (1473 hom.)
• Consequence: LILRB1 NM_001081637.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001099
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.99
• Publications: 11 publications found

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081637.3. 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
	LILRB1	NM_001081637.3	MANE Select	c.1813-7G>A		splice_region intron	N/A	NP_001075106.2
	LILRB1	NM_001388358.1		c.1813-7G>A		splice_region intron	N/A	NP_001375287.1
	LILRB1	NM_001081638.4		c.1810-7G>A		splice_region intron	N/A	NP_001075107.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB1	ENST00000324602.12	TSL:5 MANE Select	c.1813-7G>A		splice_region intron	N/A	ENSP00000315997.7
	LILRB1	ENST00000396315.5	TSL:1	c.1813-7G>A		splice_region intron	N/A	ENSP00000379608.1
	LILRB1	ENST00000396327.7	TSL:1	c.1810-7G>A		splice_region intron	N/A	ENSP00000379618.3

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 4967 AN: 70750 Hom.: 100 Cov.: 17

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0682

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0884

GnomAD2 exomes AF: 0.0458 AC: 9297 AN: 203086 AF XY: 0.0465

Gnomad AFR exome AF: 0.00870

Gnomad AMR exome AF: 0.0298

Gnomad ASJ exome AF: 0.0799

Gnomad EAS exome AF: 0.000822

Gnomad FIN exome AF: 0.0434

Gnomad NFE exome AF: 0.0540

Gnomad OTH exome AF: 0.0642

GnomAD4 exome AF: 0.0606 AC: 67946 AN: 1121136 Hom.: 1473 Cov.: 48 AF XY: 0.0615 AC XY: 33942 AN XY: 551746

African (AFR) AF: 0.00881 AC: 209 AN: 23736

American (AMR) AF: 0.0284 AC: 969 AN: 34140

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 1903 AN: 17816

East Asian (EAS) AF: 0.000752 AC: 12 AN: 15960

South Asian (SAS) AF: 0.0530 AC: 3931 AN: 74124

European-Finnish (FIN) AF: 0.0704 AC: 2493 AN: 35426

Middle Eastern (MID) AF: 0.0538 AC: 207 AN: 3846

European-Non Finnish (NFE) AF: 0.0635 AC: 55512 AN: 874618

Other (OTH) AF: 0.0653 AC: 2710 AN: 41470

GnomAD4 genome AF: 0.0702 AC: 4967 AN: 70802 Hom.: 99 Cov.: 17 AF XY: 0.0698 AC XY: 2291 AN XY: 32824

African (AFR) AF: 0.0227 AC: 374 AN: 16504

American (AMR) AF: 0.0730 AC: 348 AN: 4766

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 230 AN: 2084

East Asian (EAS) AF: 0.00309 AC: 6 AN: 1944

South Asian (SAS) AF: 0.0907 AC: 171 AN: 1886

European-Finnish (FIN) AF: 0.127 AC: 375 AN: 2960

Middle Eastern (MID) AF: 0.0682 AC: 6 AN: 88

European-Non Finnish (NFE) AF: 0.0858 AC: 3352 AN: 39056

Other (OTH) AF: 0.0866 AC: 83 AN: 958

Alfa AF: 0.0391 Hom.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.79
DANN	Benign	0.67
PhyloP100		-6.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs41308748; hg19: chr19-55148176; COSMIC: COSV61116461; COSMIC: COSV61116461;