rs1468674

chr12-9595686-A-Cchr12-9595686-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002258.3(KLRB1):c.531-265T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,982 control chromosomes in the GnomAD database, including 15,424 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 0.41 (15424 hom., cov: 31)
• Consequence: KLRB1 NM_002258.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

Genes affected

KLRB1 (HGNC:6373): (killer cell lectin like receptor B1) Natural killer (NK) cells are lymphocytes that mediate cytotoxicity and secrete cytokines after immune stimulation. Several genes of the C-type lectin superfamily, including the rodent NKRP1 family of glycoproteins, are expressed by NK cells and may be involved in the regulation of NK cell function. The KLRB1 protein contains an extracellular domain with several motifs characteristic of C-type lectins, a transmembrane domain, and a cytoplasmic domain. The KLRB1 protein is classified as a type II membrane protein because it has an external C terminus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLRB1	NM_002258.3	c.531-265T>G		intron_variant		ENST00000229402.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRB1	ENST00000229402.4	c.531-265T>G		intron_variant		1	NM_002258.3	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62552 AN: 151864 Hom.: 15423 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.412 AC: 62561 AN: 151982 Hom.: 15424 Cov.: 31 AF XY: 0.419 AC XY: 31109 AN XY: 74286

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.439

Alfa AF: 0.491 Hom.: 21413

Bravo AF: 0.391

Asia WGS AF: 0.395 AC: 1370 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.92
Dann	Benign	0.84

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

Other links and lift over

dbSNP: rs1468674; hg19: chr12-9748282;