Genetic Variant NM_006863.4:c.56C>A (chr19-54594462-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006863.4(LILRA1):c.56C>A(p.Thr19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. T19I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 37)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LILRA1
NM_006863.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.757

Publications

0 publications found

Variant links:

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]

LILRA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.07055637).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LILRA1	NM_006863.4	MANE Select	c.56C>A	p.Thr19Asn	missense	Exon 3 of 10	NP_006854.1	O75019-1
LILRA1	NM_001278319.1		c.56C>A	p.Thr19Asn	missense	Exon 2 of 7	NP_001265248.1	O75019
LILRA1	NM_001278318.2		c.56C>A	p.Thr19Asn	missense	Exon 3 of 8	NP_001265247.1	O75019-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LILRA1	ENST00000251372.8	TSL:1 MANE Select	c.56C>A	p.Thr19Asn	missense	Exon 3 of 10	ENSP00000251372.3	O75019-1
LILRA1	ENST00000453777.1	TSL:1	c.56C>A	p.Thr19Asn	missense	Exon 3 of 8	ENSP00000413715.1	O75019-2
LILRA1	ENST00000473156.5	TSL:1	n.222C>A		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251424

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461790

Hom.:

Cov.:

115

AF XY:

0.00000138

AC XY:

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.018

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0097

M_CAP

Benign

0.0014

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

PhyloP100

-0.76

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.032

Sift

Benign

0.12

Sift4G

Benign

0.11

Polyphen

0.13

Vest4

0.14

MutPred

0.35

Gain of sheet (P = 0.1208)

MVP

0.15

MPC

0.032

ClinPred

0.036

GERP RS

-0.20

Varity_R

0.19

gMVP

0.063

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over