19-54336877-A-G

Variant names:

• chr19-54336877-A-G
• rs568171065
• NM_012276.5:c.1219T>C

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.1219T>C​(p.Ser407Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 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. S407T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: LILRA4 NM_012276.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• 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=0.17859831).

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.1219T>C	p.Ser407Pro	missense	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.1219T>C	p.Ser407Pro	missense	Exon 6 of 8	ENSP00000291759.4	P59901-1
	LILRA4	ENST00000595581.1	TSL:3	n.316T>C		non_coding_transcript_exon	Exon 2 of 2	ENSP00000471722.1	A0A075B7A5
	ENSG00000275210	ENST00000616950.1	TSL:3	n.292T>C		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1377234 Hom.: 0 Cov.: 136 AF XY: 0.00000146 AC XY: 1 AN XY: 685642

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31302

American (AMR) AF: 0.00 AC: 0 AN: 40832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24602

East Asian (EAS) AF: 0.00 AC: 0 AN: 38482

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5386

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1047262

Other (OTH) AF: 0.00 AC: 0 AN: 57028

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.3
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.059
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.28
MutPred		0.36		Loss of sheet (P = 0.0315)
MVP		0.30
MPC		0.17
ClinPred		0.91	D
GERP RS		2.4
gMVP		0.79
Mutation Taster		=87/13	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

Other links and lift over

dbSNP: rs568171065; hg19: chr19-54848148;