rs142580255

Variant names:

• chr19-54337487-A-G
• rs142580255
• NM_012276.5:c.865T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-54337487-A-G
• chr19-54337487-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_012276.5(LILRA4):​c.865T>C​(p.Tyr289His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,612,354 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: LILRA4 NM_012276.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.850

Genes affected

LILRA4 (HGNC:15503): (leukocyte immunoglobulin like receptor A4) This gene encodes an immunoglobulin-like cell surface protein that is expressed predominantly on plasmacytoid dendritic cells (PDCs) and modulates the function of these cells in the immune response. Expression of this gene is downregulated by interleukin 3 (IL3). This gene is one of a cluster of highly related genes located at chromosomal region 19q13.4. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00918898).
• BP6: Variant 19-54337487-A-G is Benign according to our data. Variant chr19-54337487-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3118762.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRA4	NM_012276.5	c.865T>C	p.Tyr289His	missense_variant	Exon 5 of 8	ENST00000291759.5	NP_036408.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRA4	ENST00000291759.5	c.865T>C	p.Tyr289His	missense_variant	Exon 5 of 8	2	NM_012276.5	ENSP00000291759.4
LILRA4	ENST00000595581.1	n.-39T>C		upstream_gene_variant		3		ENSP00000471722.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152036 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000164 AC: 41 AN: 250376 AF XY: 0.000184

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000599

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000973

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000205 AC: 300 AN: 1460202 Hom.: 1 Cov.: 97 AF XY: 0.000202 AC XY: 147 AN XY: 726412

African (AFR) AF: 0.000120 AC: 4 AN: 33422

American (AMR) AF: 0.000157 AC: 7 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.000932 AC: 37 AN: 39698

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4676

European-Non Finnish (NFE) AF: 0.000186 AC: 207 AN: 1111824

Other (OTH) AF: 0.000249 AC: 15 AN: 60250

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152152 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74404

African (AFR) AF: 0.0000963 AC: 4 AN: 41536

American (AMR) AF: 0.000196 AC: 3 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5138

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67954

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000114 Hom.: 0

Bravo AF: 0.000196

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.011
DANN	Benign	0.82
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0014	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.0092	T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	3.4	N
REVEL	Benign	0.019
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.23
MVP		0.088
MPC		0.097
ClinPred		0.21	T
GERP RS		0.26
gMVP		0.21
Mutation Taster		=100/0	polymorphism

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: rs142580255; hg19: chr19-54848758;