19-54595118-C-T

Variant names:

• chr19-54595118-C-T
• rs1295352284
• NM_006863.4:c.377C>T

Variant summary

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

The NM_006863.4(LILRA1):​c.377C>T​(p.Thr126Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T126S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: LILRA1 NM_006863.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.63
• Publications: 1 publications found

Genes affected

LILRA1 (HGNC:6602): (leukocyte immunoglobulin like receptor A1) This gene encodes an activating member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein is predominantly expressed in B cells, interacts with major histocompatibility complex class I ligands, and contributes to the regulation of immune responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

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=0.11979571).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006863.4. 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
	LILRA1	NM_006863.4	MANE Select	c.377C>T	p.Thr126Ile	missense	Exon 5 of 10	NP_006854.1	O75019-1
	LILRA1	NM_001278319.1		c.377C>T	p.Thr126Ile	missense	Exon 4 of 7	NP_001265248.1	O75019
	LILRA1	NM_001278318.2		c.377C>T	p.Thr126Ile	missense	Exon 5 of 8	NP_001265247.1	O75019-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRA1	ENST00000251372.8	TSL:1 MANE Select	c.377C>T	p.Thr126Ile	missense	Exon 5 of 10	ENSP00000251372.3	O75019-1
	LILRA1	ENST00000453777.1	TSL:1	c.377C>T	p.Thr126Ile	missense	Exon 5 of 8	ENSP00000413715.1	O75019-2
	LILRA1	ENST00000473156.5	TSL:1	n.543C>T		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250784 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461448 Hom.: 0 Cov.: 83 AF XY: 0.0000330 AC XY: 24 AN XY: 726988

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111730

Other (OTH) AF: 0.0000331 AC: 2 AN: 60366

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0062	N
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-1.6
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.062
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.014	D
Polyphen		0.49	P
Vest4		0.067
MutPred		0.41		Loss of glycosylation at T126 (P = 0.0261)
MVP		0.20
MPC		0.15
ClinPred		0.69	D
GERP RS		-4.5
Varity_R		0.18
gMVP		0.074
Mutation Taster		=96/4	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: rs1295352284; hg19: chr19-55106583;