19-54631605-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001081637.3(LILRB1):c.176G>A(p.Arg59His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (0 hom., cov: 48)
  • Exomes 𝑓: 0.47 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -9.37

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028176844).
• BP6: Variant 19-54631605-G-A is Benign according to our data. Variant chr19-54631605-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2341195.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LILRB1	NM_001081637.3	c.176G>A	p.Arg59His	missense_variant	4/15	ENST00000324602.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LILRB1	ENST00000324602.12	c.176G>A	p.Arg59His	missense_variant	4/15	5	NM_001081637.3	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 66749 AN: 140752 Hom.: 0 Cov.: 48 FAILED QC

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.482

GnomAD3 exomes AF: 0.000115 AC: 29 AN: 251394 Hom.: 0 AF XY: 0.0000957 AC XY: 13 AN XY: 135842

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000652

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.465 AC: 626918 AN: 1346820 Hom.: 4 Cov.: 142 AF XY: 0.466 AC XY: 312371 AN XY: 669860

Gnomad4 AFR exome AF: 0.494

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.474 AC: 66804 AN: 140860 Hom.: 0 Cov.: 48 AF XY: 0.472 AC XY: 32481 AN XY: 68770

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.482

Alfa AF: 0.225 Hom.: 0

ExAC AF: 0.000107 AC: 13

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.0020
Dann	Benign	0.47
DEOGEN2	Benign	0.0089	T;T;.;.;T;.;.
Eigen	Benign	-2.7
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.078	T;T;T;T;T;T;.
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.028	T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	1.4	N;N;N;N;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.95	T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0060	.;.;.;.;.;B;.
Vest4		0.073
MVP		0.085
MPC		0.068
ClinPred		0.048	T
GERP RS		-4.2
gMVP		0.16

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: rs774715846; hg19: chr19-55143056; COSMIC: COSV61116523; COSMIC: COSV61116523;