rs12821842

Variant names:

• chr12-8956388-G-A
• rs12821842
• NM_001329101.2:c.-156+6152G>A

Variant summary

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

The NM_001329101.2(KLRG1):​c.-156+6152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,038 control chromosomes in the GnomAD database, including 11,379 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 0.37 (11379 hom., cov: 32)
• Consequence: KLRG1 NM_001329101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 13 publications found

Genes affected

KLRG1 (HGNC:6380): (killer cell lectin like receptor G1) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules. [provided by RefSeq, Jun 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRG1	NM_001329101.2	c.-156+6152G>A		intron_variant	Intron 1 of 4		NP_001316030.1
KLRG1	NM_001329102.2	c.-290+6152G>A		intron_variant	Intron 1 of 5		NP_001316031.1
KLRG1	NM_001329103.2	c.-156+6203G>A		intron_variant	Intron 1 of 4		NP_001316032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRG1	ENST00000539240.5	c.-156+6152G>A		intron_variant	Intron 1 of 4	3		ENSP00000445627.1
KLRG1	ENST00000538029.1	n.112+6152G>A		intron_variant	Intron 1 of 2	2
KLRG1	ENST00000544226.5	n.130+6152G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55805 AN: 151920 Hom.: 11374 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.367 AC: 55831 AN: 152038 Hom.: 11379 Cov.: 32 AF XY: 0.370 AC XY: 27463 AN XY: 74310

African (AFR) AF: 0.183 AC: 7604 AN: 41502

American (AMR) AF: 0.380 AC: 5808 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1645 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2057 AN: 5140

South Asian (SAS) AF: 0.462 AC: 2227 AN: 4818

European-Finnish (FIN) AF: 0.476 AC: 5032 AN: 10566

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30237 AN: 67938

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.426 Hom.: 24064

Bravo AF: 0.353

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12821842; hg19: chr12-9108984;