19-54333765-G-A

Variant names:

• chr19-54333765-G-A
• NM_012276.5:c.1307C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012276.5(LILRA4):​c.1307C>T​(p.Ala436Val) 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 benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LILRA4 NM_012276.5 missense, splice_region
• Scores: Splicing: ADA: 0.0008383
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.114
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120719045).

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.1307C>T	p.Ala436Val	missense splice_region	Exon 8 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.1307C>T	p.Ala436Val	missense splice_region	Exon 8 of 8	ENSP00000291759.4	P59901-1
	ENSG00000275210	ENST00000616950.1	TSL:3	n.379+150C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.8
DANN	Benign	0.93
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.013	N
M_CAP	Benign	0.00077	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.11
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.023
Sift	Benign	0.031	D
Sift4G	Benign	0.11	T
Vest4		0.18
MutPred		0.30		Gain of sheet (P = 0.0344)
MVP		0.095
MPC		0.19
ClinPred		0.12	T
GERP RS		-2.1
gMVP		0.11
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00084
dbscSNV1_RF	Benign	0.20
SpliceAI score (max)		0.030		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

hg19: chr19-54845036;