chr19-54734271-C-T

Variant names:

• chr19-54734271-C-T
• rs587560
• NM_153443.5:c.950-982C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153443.5(KIR3DL3):​c.950-982C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 149,166 control chromosomes in the GnomAD database, including 6,895 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 0.30 (6895 hom., cov: 27)
• Consequence: KIR3DL3 NM_153443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 4 publications found

Genes affected

KIR3DL3 (HGNC:16312): (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 3) 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. [provided by RefSeq, Jul 2008]

ENSG00000215765 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIR3DL3	NM_153443.5	c.950-982C>T		intron_variant	Intron 5 of 7	ENST00000291860.2	NP_703144.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIR3DL3	ENST00000291860.2	c.950-982C>T		intron_variant	Intron 5 of 7	1	NM_153443.5	ENSP00000291860.1
ENSG00000215765	ENST00000400864.3	n.35+9741C>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.299 AC: 44573 AN: 149046 Hom.: 6875 Cov.: 27

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 44633 AN: 149166 Hom.: 6895 Cov.: 27 AF XY: 0.300 AC XY: 21823 AN XY: 72760

African (AFR) AF: 0.317 AC: 12804 AN: 40418

American (AMR) AF: 0.322 AC: 4820 AN: 14958

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1215 AN: 3412

East Asian (EAS) AF: 0.121 AC: 624 AN: 5140

South Asian (SAS) AF: 0.393 AC: 1819 AN: 4624

European-Finnish (FIN) AF: 0.237 AC: 2460 AN: 10378

Middle Eastern (MID) AF: 0.344 AC: 99 AN: 288

European-Non Finnish (NFE) AF: 0.297 AC: 19922 AN: 66992

Other (OTH) AF: 0.307 AC: 631 AN: 2058

Alfa AF: 0.302 Hom.: 5425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.9
DANN	Benign	0.36
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs587560; hg19: chr19-55245738;