rs568171065

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-54336877-A-T
• chr19-54336877-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012276.5(LILRA4):​c.1219T>A​(p.Ser407Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.0035 (0 hom., cov: 33)
  • Exomes 𝑓: 0.021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRA4 NM_012276.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009393901).

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>A	p.Ser407Thr	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>A	p.Ser407Thr	missense	Exon 6 of 8	ENSP00000291759.4	P59901-1
	LILRA4	ENST00000595581.1	TSL:3	n.316T>A		non_coding_transcript_exon	Exon 2 of 2	ENSP00000471722.1	A0A075B7A5
	ENSG00000275210	ENST00000616950.1	TSL:3	n.292T>A		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 418 AN: 119036 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00496

Gnomad AMI AF: 0.00434

Gnomad AMR AF: 0.00384

Gnomad ASJ AF: 0.00154

Gnomad EAS AF: 0.00268

Gnomad SAS AF: 0.00784

Gnomad FIN AF: 0.00487

Gnomad MID AF: 0.00410

Gnomad NFE AF: 0.00220

Gnomad OTH AF: 0.00635

GnomAD2 exomes AF: 0.000123 AC: 31 AN: 251416 AF XY: 0.000125

Gnomad AFR exome AF: 0.000739

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: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0206 AC: 19473 AN: 945454 Hom.: 0 Cov.: 136 AF XY: 0.0268 AC XY: 12416 AN XY: 462446

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

African (AFR) AF: 0.0130 AC: 289 AN: 22218

American (AMR) AF: 0.0429 AC: 1176 AN: 27412

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 1087 AN: 15774

East Asian (EAS) AF: 0.00794 AC: 267 AN: 33620

South Asian (SAS) AF: 0.0892 AC: 3224 AN: 36124

European-Finnish (FIN) AF: 0.0388 AC: 1382 AN: 35624

Middle Eastern (MID) AF: 0.0921 AC: 295 AN: 3204

European-Non Finnish (NFE) AF: 0.0150 AC: 10955 AN: 730686

Other (OTH) AF: 0.0196 AC: 798 AN: 40792

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00351 AC: 418 AN: 119176 Hom.: 0 Cov.: 33 AF XY: 0.00413 AC XY: 239 AN XY: 57850

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

African (AFR) AF: 0.00494 AC: 152 AN: 30776

American (AMR) AF: 0.00383 AC: 47 AN: 12262

Ashkenazi Jewish (ASJ) AF: 0.00154 AC: 4 AN: 2594

East Asian (EAS) AF: 0.00268 AC: 12 AN: 4474

South Asian (SAS) AF: 0.00780 AC: 27 AN: 3462

European-Finnish (FIN) AF: 0.00487 AC: 42 AN: 8616

Middle Eastern (MID) AF: 0.00439 AC: 1 AN: 228

European-Non Finnish (NFE) AF: 0.00220 AC: 120 AN: 54474

Other (OTH) AF: 0.00626 AC: 10 AN: 1598

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.126 Hom.: 0

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.000273

EpiControl AF: 0.000178

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	0.089
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.97
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.039
Sift	Benign	0.079	T
Sift4G	Benign	0.074	T
Vest4		0.23
MVP		0.22
MPC		0.11
ClinPred		0.053	T
GERP RS		2.4
gMVP		0.48
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: rs568171065; hg19: chr19-54848148; COSMIC: COSV52491226; COSMIC: COSV52491226;