Variant chr19-54819832-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000391728.8(KIR3DL1):c.475G>T(p.Gly159Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,609,646 control chromosomes in the GnomAD database, including 41,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.19 ( 3168 hom., cov: 33)

Exomes 𝑓: 0.22 ( 38476 hom. )

Consequence

KIR3DL1
ENST00000391728.8 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.307

Variant links:

Genes affected

KIR3DL1 (HGNC:6338): (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1) Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. [provided by RefSeq, Jul 2008]

KIR3DL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044963956).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIR3DL1	NM_013289.4 linkuse as main transcript	c.475G>T	p.Gly159Trp	missense_variant	4/9		NP_037421.2	P43629-1Q5UCE2Q8N6C9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
KIR3DL1	ENST00000391728.8 linkuse as main transcript	c.475G>T	p.Gly159Trp	missense_variant	4/9	1	ENSP00000375608.4	P43629-1
KIR3DL1	ENST00000326542.11 linkuse as main transcript	c.475G>T	p.Gly159Trp	missense_variant	4/8	1	ENSP00000326868.7	W5QJC1
KIR3DL1	ENST00000358178.4 linkuse as main transcript	c.190G>T	p.Gly64Trp	missense_variant	3/8	1	ENSP00000350901.4	P43629-2

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28181

AN:

151158

Hom.:

3163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0750

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.223

AC:

325078

AN:

1458374

Hom.:

38476

Cov.:

AF XY:

0.226

AC XY:

164196

AN XY:

725586

show subpopulations

Gnomad4 AFR exome

AF:

0.0645

Gnomad4 AMR exome

AF:

0.251

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.206

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.260

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.186

AC:

28192

AN:

151272

Hom.:

3168

Cov.:

AF XY:

0.196

AC XY:

14456

AN XY:

73896

show subpopulations

Gnomad4 AFR

AF:

0.0748

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.322

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.143

Hom.:

419

Bravo

AF:

0.175

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Keratoconus

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Institute of Human Genetics, Polish Academy of Sciences

Apr 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.092

T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.021

M_CAP

Benign

0.0015

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.5

H;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Benign

0.13

Sift

Benign

0.033

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.78

P;.;.

Vest4

0.33

MutPred

0.41

Loss of disorder (P = 0.0104);Loss of disorder (P = 0.0104);.;

MVP

0.088

MPC

0.70

ClinPred

0.47

GERP RS

1.4

Varity_R

0.20

gMVP

0.071

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over