12-8950652-G-T

Position:

• chr12-8950652-G-T

Variant summary

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

The NM_001329101.2(KLRG1):​c.-156+416G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,718 control chromosomes in the GnomAD database, including 38,375 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 0.69 (38375 hom., cov: 29)
• Consequence: KLRG1 NM_001329101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

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]

KLRG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRG1	NM_001329101.2	c.-156+416G>T		intron_variant			NP_001316030.1
KLRG1	NM_001329102.2	c.-290+416G>T		intron_variant			NP_001316031.1
KLRG1	NM_001329103.2	c.-156+467G>T		intron_variant			NP_001316032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG1	ENST00000539240.5	c.-156+416G>T		intron_variant		3		ENSP00000445627.1
KLRG1	ENST00000538029.1	n.112+416G>T		intron_variant		2
KLRG1	ENST00000544226.5	n.130+416G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105139 AN: 151600 Hom.: 38353 Cov.: 29

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.693 AC: 105207 AN: 151718 Hom.: 38375 Cov.: 29 AF XY: 0.693 AC XY: 51361 AN XY: 74136

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.684

Alfa AF: 0.696 Hom.: 2393

Bravo AF: 0.678

Asia WGS AF: 0.633 AC: 2202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1805754; hg19: chr12-9103248;