chr19-54632196-A-T

Position:

• chr19-54632196-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001081637.3(LILRB1):​c.620A>T​(p.Glu207Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.015 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034101337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB1	NM_001081637.3	c.620A>T	p.Glu207Val	missense_variant	5/15	ENST00000324602.12	NP_001075106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB1	ENST00000324602.12	c.620A>T	p.Glu207Val	missense_variant	5/15	5	NM_001081637.3	ENSP00000315997.7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 232 AN: 112768 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00310

Gnomad ASJ AF: 0.00119

Gnomad EAS AF: 0.00163

Gnomad SAS AF: 0.00443

Gnomad FIN AF: 0.00133

Gnomad MID AF: 0.00625

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00204

GnomAD3 exomes AF: 0.0000318 AC: 8 AN: 251316 Hom.: 1 AF XY: 0.0000368 AC XY: 5 AN XY: 135810

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.0146 AC: 10761 AN: 739108 Hom.: 1 Cov.: 100 AF XY: 0.0166 AC XY: 6096 AN XY: 366928

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.0523

Gnomad4 ASJ exome AF: 0.0805

Gnomad4 EAS exome AF: 0.000823

Gnomad4 SAS exome AF: 0.0654

Gnomad4 FIN exome AF: 0.00685

Gnomad4 NFE exome AF: 0.00887

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00206 AC: 233 AN: 112848 Hom.: 0 Cov.: 32 AF XY: 0.00230 AC XY: 128 AN XY: 55568

Gnomad4 AFR AF: 0.00326

Gnomad4 AMR AF: 0.00310

Gnomad4 ASJ AF: 0.00119

Gnomad4 EAS AF: 0.00163

Gnomad4 SAS AF: 0.00442

Gnomad4 FIN AF: 0.00133

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.00202

Alfa AF: 0.00430 Hom.: 0

ExAC AF: 0.0000412 AC: 5

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

Oct 12, 2024

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	-0.58	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.15
DANN	Benign	0.35
DEOGEN2	Benign	0.0035	T;T;.;.;T;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00089	N
LIST_S2	Benign	0.028	T;T;T;T;T;T;.
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.034	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	5.0	N;N;N;N;N;N;N
REVEL	Benign	0.010
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0	.;.;.;.;.;B;.
Vest4		0.12
MVP		0.088
MPC		0.064
ClinPred		0.025	T
GERP RS		-1.0
gMVP		0.097

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs775869419; hg19: chr19-55143647;