Variant chr19-54813180-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001080772.2(KIR2DL4):c.762T>C(p.Phe254Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,362,288 control chromosomes in the GnomAD database, including 208,821 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 17084 hom., cov: 18)

Exomes 𝑓: 0.52 ( 191737 hom. )

Consequence

KIR2DL4
NM_001080772.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.616

Variant links:

Genes affected

KIR2DL4 (HGNC:6332): (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4) 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. This gene is one of the "framework" loci that is present on all haplotypes. Alternate alleles of this gene are represented on multiple alternate reference loci (ALT_REF_LOCs). Alternative splicing results in multiple transcript variants, some of which may not be annotated on the primary reference assembly. [provided by RefSeq, Jul 2016]

KIR2DL4 links:

KIR2DL4 (HGNC:):

KIR2DL4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIR2DL4	NM_001080770.2 linkuse as main transcript	c.707-510T>C		intron_variant		ENST00000345540.10	NP_001074239.1	A0A376A929
KIR2DL4	NM_001080772.2 linkuse as main transcript	c.762T>C	p.Phe254Phe	synonymous_variant	6/8		NP_001074241.1	A0A0B4J1S6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIR2DL4	ENST00000345540.10 linkuse as main transcript	c.707-510T>C		intron_variant		1	NM_001080770.2	ENSP00000339634.5		Q99706-3

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

61234

AN:

118196

Hom.:

17063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.539

Gnomad NFE

AF:

0.462

Gnomad OTH

AF:

0.525

GnomAD3 exomes

AF:

0.0115

AC:

1724

AN:

150032

Hom.:

664

AF XY:

0.00887

AC XY:

734

AN XY:

82756

show subpopulations

Gnomad AFR exome

AF:

0.0335

Gnomad AMR exome

AF:

0.00766

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.0240

Gnomad SAS exome

AF:

0.00962

Gnomad FIN exome

AF:

0.00373

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00772

GnomAD4 exome

AF:

0.517

AC:

643528

AN:

1244026

Hom.:

191737

Cov.:

AF XY:

0.519

AC XY:

322292

AN XY:

620722

show subpopulations

Gnomad4 AFR exome

AF:

0.705

Gnomad4 AMR exome

AF:

0.691

Gnomad4 ASJ exome

AF:

0.552

Gnomad4 EAS exome

AF:

0.831

Gnomad4 SAS exome

AF:

0.609

Gnomad4 FIN exome

AF:

0.498

Gnomad4 NFE exome

AF:

0.484

Gnomad4 OTH exome

AF:

0.540

GnomAD4 genome

AF:

0.518

AC:

61276

AN:

118262

Hom.:

17084

Cov.:

AF XY:

0.517

AC XY:

29189

AN XY:

56474

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.430

Gnomad4 NFE

AF:

0.462

Gnomad4 OTH

AF:

0.527

Alfa

AF:

0.533

Hom.:

5811

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.39

Position offset: 48

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over