Variant 19-54803871-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001080770.2(KIR2DL4):c.41-20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,606,390 control chromosomes in the GnomAD database, including 41,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.19 ( 3257 hom., cov: 28)

Exomes 𝑓: 0.22 ( 38607 hom. )

Consequence

KIR2DL4
NM_001080770.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.313

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-54803871-A-C is Benign according to our data. Variant chr19-54803871-A-C is described in ClinVar as [Benign]. Clinvar id is 1339510.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 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.41-20A>C		intron_variant		ENST00000345540.10	NP_001074239.1
KIR2DL4	NM_001080772.2 linkuse as main transcript	c.41-20A>C		intron_variant			NP_001074241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIR2DL4	ENST00000345540.10 linkuse as main transcript	c.41-20A>C		intron_variant		1	NM_001080770.2	ENSP00000339634	A2	Q99706-3

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

28653

AN:

149602

Hom.:

3252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0838

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.224

AC:

326520

AN:

1456678

Hom.:

38607

Cov.:

AF XY:

0.227

AC XY:

164810

AN XY:

724756

show subpopulations

Gnomad4 AFR exome

AF:

0.0728

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.235

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.226

GnomAD4 genome

AF:

0.191

AC:

28665

AN:

149712

Hom.:

3257

Cov.:

AF XY:

0.201

AC XY:

14648

AN XY:

73032

show subpopulations

Gnomad4 AFR

AF:

0.0836

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.325

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.193

Hom.:

292

Bravo

AF:

0.180

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pathology and Clinical Laboratory Medicine, King Fahad Medical City

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.3

DANN

Benign

0.70

La Branchor

0.89

BranchPoint Hunter

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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