chr19-54594261-C-T

Variant names:

• chr19-54594261-C-T
• rs765870298
• NM_006863.4:c.17C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006863.4(LILRA1):​c.17C>T​(p.Thr6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,611,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. T6K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: LILRA1 NM_006863.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05621159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRA1	NM_006863.4	c.17C>T	p.Thr6Ile	missense_variant	Exon 2 of 10	ENST00000251372.8	NP_006854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRA1	ENST00000251372.8	c.17C>T	p.Thr6Ile	missense_variant	Exon 2 of 10	1	NM_006863.4	ENSP00000251372.3

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000811 AC: 2 AN: 246486 Hom.: 0 AF XY: 0.00000749 AC XY: 1 AN XY: 133450

Gnomad AFR exome AF: 0.0000655

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459562 Hom.: 0 Cov.: 56 AF XY: 0.00000275 AC XY: 2 AN XY: 726186

Gnomad4 AFR exome AF: 0.0000606

Gnomad4 AMR exome AF: 0.0000453

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152050 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74268

Gnomad4 AFR AF: 0.000266

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000264

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0062	N
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.034
Sift	Uncertain	0.023	D;T
Sift4G	Benign	0.24	T;T
Polyphen		0.052	B;P
Vest4		0.14
MutPred		0.50		Loss of disorder (P = 0.0525);Loss of disorder (P = 0.0525);
MVP		0.15
MPC		0.033
ClinPred		0.096	T
GERP RS		0.031
Varity_R		0.046
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765870298; hg19: chr19-55105726;