12-8951069-T-G

Variant names:

• chr12-8951069-T-G
• rs933462
• NM_001329101.2:c.-156+833T>G

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+833T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,914 control chromosomes in the GnomAD database, including 11,104 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 0.36 (11104 hom., cov: 32)
• Consequence: KLRG1 NM_001329101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329101.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	NM_001329101.2		c.-156+833T>G		intron	N/A	NP_001316030.1
	KLRG1	NM_001329102.2		c.-290+833T>G		intron	N/A	NP_001316031.1
	KLRG1	NM_001329103.2		c.-156+884T>G		intron	N/A	NP_001316032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	ENST00000539240.5	TSL:3	c.-156+833T>G		intron	N/A	ENSP00000445627.1
	KLRG1	ENST00000538029.1	TSL:2	n.112+833T>G		intron	N/A
	KLRG1	ENST00000544226.5	TSL:3	n.130+833T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54309 AN: 151796 Hom.: 11100 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.358 AC: 54321 AN: 151914 Hom.: 11104 Cov.: 32 AF XY: 0.360 AC XY: 26726 AN XY: 74202

African (AFR) AF: 0.150 AC: 6208 AN: 41412

American (AMR) AF: 0.376 AC: 5752 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2081 AN: 5174

South Asian (SAS) AF: 0.462 AC: 2226 AN: 4814

European-Finnish (FIN) AF: 0.476 AC: 4996 AN: 10502

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30214 AN: 67954

Other (OTH) AF: 0.371 AC: 780 AN: 2104

Alfa AF: 0.410 Hom.: 16773

Bravo AF: 0.342

Asia WGS AF: 0.417 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.78
PhyloP100		0.69

Splicing

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

Other links and lift over

dbSNP: rs933462; hg19: chr12-9103665;