19-54336897-C-T

Variant names:

• chr19-54336897-C-T
• rs762916224
• NM_012276.5:c.1199G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012276.5(LILRA4):​c.1199G>A​(p.Ser400Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 152,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRA4 NM_012276.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10535839).

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.1199G>A	p.Ser400Asn	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.1199G>A	p.Ser400Asn	missense	Exon 6 of 8	ENSP00000291759.4	P59901-1
	LILRA4	ENST00000595581.1	TSL:3	n.296G>A		non_coding_transcript_exon	Exon 2 of 2	ENSP00000471722.1	A0A075B7A5
	ENSG00000275210	ENST00000616950.1	TSL:3	n.272G>A		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152226 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000437 AC: 11 AN: 251438 AF XY: 0.0000589

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000369 AC: 54 AN: 1461636 Hom.: 0 Cov.: 137 AF XY: 0.0000371 AC XY: 27 AN XY: 727138

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

African (AFR) AF: 0.0000897 AC: 3 AN: 33456

American (AMR) AF: 0.000134 AC: 6 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1111802

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

⚠️ 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 AF: 0.000125 AC: 19 AN: 152226 Hom.: 0 Cov.: 34 AF XY: 0.000134 AC XY: 10 AN XY: 74368

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

African (AFR) AF: 0.000217 AC: 9 AN: 41450

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000738601), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000190 Hom.: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.11
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.92
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0095	N
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
PhyloP100		-1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.028
Sift	Benign	0.28	T
Sift4G	Benign	0.24	T
Vest4		0.21
MVP		0.11
MPC		0.16
ClinPred		0.031	T
GERP RS		-4.0
gMVP		0.11
Mutation Taster		=97/3	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: rs762916224; hg19: chr19-54848168;