NM_012276.5:c.953G>T

Variant names:

• chr19-54337143-C-A
• rs773279262
• NM_012276.5:c.953G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012276.5(LILRA4):​c.953G>T​(p.Gly318Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G318E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LILRA4 NM_012276.5 missense, splice_region
• Scores: Splicing: ADA: 0.9774
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 2 publications found

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]

ENSG00000275210 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012276.5. 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
	LILRA4	NM_012276.5	MANE Select	c.953G>T	p.Gly318Val	missense splice_region	Exon 6 of 8	NP_036408.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRA4	ENST00000291759.5	TSL:2 MANE Select	c.953G>T	p.Gly318Val	missense splice_region	Exon 6 of 8	ENSP00000291759.4	P59901-1
	LILRA4	ENST00000595581.1	TSL:3	n.50G>T		splice_region non_coding_transcript_exon	Exon 2 of 2	ENSP00000471722.1	A0A075B7A5
	ENSG00000275210	ENST00000616950.1	TSL:3	n.26G>T		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.98
Eigen	Benign	0.030
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.047	N
M_CAP	Benign	0.0022	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.1	T
PhyloP100		-0.62
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.076
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.25
MutPred		0.80		Loss of disorder (P = 0.0662)
MVP		0.39
MPC		0.44
ClinPred		1.0	D
GERP RS		2.7
gMVP		0.50
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.75
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

Other links and lift over

dbSNP: rs773279262; hg19: chr19-54848414; COSMIC: COSV52494773; COSMIC: COSV52494773;