19-54741104-G-T

Variant names:

• chr19-54741104-G-T
• rs1639427
• NM_015868.3:c.71-876G>T

Variant summary

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

The NM_015868.3(KIR2DL3):​c.71-876G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 148,416 control chromosomes in the GnomAD database, including 5,991 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 0.28 (5991 hom., cov: 28)
• Consequence: KIR2DL3 NM_015868.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 1 publications found

Genes affected

KIR2DL3 (HGNC:6331): (killer cell immunoglobulin like receptor, two 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. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIR2DL3	NM_015868.3	c.71-876G>T		intron_variant	Intron 2 of 7	ENST00000342376.4	NP_056952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIR2DL3	ENST00000342376.4	c.71-876G>T		intron_variant	Intron 2 of 7	1	NM_015868.3	ENSP00000342215.3
ENSG00000215765	ENST00000400864.3	n.35+16574G>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 41974 AN: 148304 Hom.: 5983 Cov.: 28

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.283 AC: 42015 AN: 148416 Hom.: 5991 Cov.: 28 AF XY: 0.284 AC XY: 20588 AN XY: 72442

African (AFR) AF: 0.263 AC: 10516 AN: 40046

American (AMR) AF: 0.313 AC: 4595 AN: 14698

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1212 AN: 3392

East Asian (EAS) AF: 0.120 AC: 613 AN: 5096

South Asian (SAS) AF: 0.386 AC: 1783 AN: 4622

European-Finnish (FIN) AF: 0.233 AC: 2408 AN: 10340

Middle Eastern (MID) AF: 0.339 AC: 97 AN: 286

European-Non Finnish (NFE) AF: 0.298 AC: 19933 AN: 66978

Other (OTH) AF: 0.300 AC: 617 AN: 2054

Alfa AF: 0.279 Hom.: 499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.28
PhyloP100		-0.39
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: rs1639427; hg19: chr19-55252550;