12-9602982-G-A

Position:

• chr12-9602982-G-A

Variant summary

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

The NM_002258.3(KLRB1):​c.86-1383C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,934 control chromosomes in the GnomAD database, including 8,801 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 0.32 (8801 hom., cov: 31)
• Consequence: KLRB1 NM_002258.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRB1	NM_002258.3	c.86-1383C>T		intron_variant		ENST00000229402.4	NP_002249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRB1	ENST00000229402.4	c.86-1383C>T		intron_variant		1	NM_002258.3	ENSP00000229402	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48917 AN: 151816 Hom.: 8804 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.322 AC: 48934 AN: 151934 Hom.: 8801 Cov.: 31 AF XY: 0.330 AC XY: 24481 AN XY: 74258

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.355

Alfa AF: 0.347 Hom.: 5384

Bravo AF: 0.314

Asia WGS AF: 0.448 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.46

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: rs4763655; hg19: chr12-9755578;