rs2889717

Variant names:

• chr12-9134205-T-C
• rs2889717
• ENST00000839050.1:n.81-881T>C

Variant summary

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

The ENST00000839050.1(ENSG00000309149):​n.81-881T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 152,254 control chromosomes in the GnomAD database, including 160 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 0.022 (160 hom., cov: 32)
• Consequence: ENSG00000309149 ENST00000839050.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 4 publications found

Genes affected

ENSG00000309149 (HGNC:):

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRG1	XM_017018684.2	c.*34-881T>C		intron_variant	Intron 6 of 6		XP_016874173.1
KLRG1	XM_017018685.2	c.*33+76039T>C		intron_variant	Intron 6 of 6		XP_016874174.1
KLRG1	XM_047428074.1	c.*34-59850T>C		intron_variant	Intron 6 of 6		XP_047284030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000309149	ENST00000839050.1	n.81-881T>C		intron_variant	Intron 1 of 1
ENSG00000309149	ENST00000839051.1	n.335+5570T>C		intron_variant	Intron 1 of 1
ENSG00000309236	ENST00000839766.1	n.*183A>G		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3348 AN: 152136 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00700

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0221 AC: 3359 AN: 152254 Hom.: 160 Cov.: 32 AF XY: 0.0252 AC XY: 1874 AN XY: 74454

African (AFR) AF: 0.00522 AC: 217 AN: 41564

American (AMR) AF: 0.0826 AC: 1264 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.149 AC: 769 AN: 5176

South Asian (SAS) AF: 0.0841 AC: 405 AN: 4816

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00699 AC: 475 AN: 68000

Other (OTH) AF: 0.0317 AC: 67 AN: 2116

Alfa AF: 0.0110 Hom.: 5

Bravo AF: 0.0290

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.45
PhyloP100		0.084

Splicing

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

Other links and lift over

dbSNP: rs2889717; hg19: chr12-9286801;