12-8984026-A-T

Variant names:

• chr12-8984026-A-T
• rs1121401
• NM_001329101.2:c.-155-8180A>T

Variant summary

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

The NM_001329101.2(KLRG1):​c.-155-8180A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 151,952 control chromosomes in the GnomAD database, including 48,921 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 0.80 (48921 hom., cov: 29)
• Consequence: KLRG1 NM_001329101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 3 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.832 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	NM_001329101.2		c.-155-8180A>T		intron	N/A	NP_001316030.1
	KLRG1	NM_001329102.2		c.-289-6186A>T		intron	N/A	NP_001316031.1
	KLRG1	NM_001329103.2		c.-155-8180A>T		intron	N/A	NP_001316032.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	ENST00000539240.5	TSL:3	c.-155-8180A>T		intron	N/A	ENSP00000445627.1	F5H207
	KLRG1	ENST00000538029.1	TSL:2	n.113-24949A>T		intron	N/A
	KLRG1	ENST00000541957.1	TSL:4	n.248-6186A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121332 AN: 151834 Hom.: 48868 Cov.: 29

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.799 AC: 121446 AN: 151952 Hom.: 48921 Cov.: 29 AF XY: 0.795 AC XY: 59047 AN XY: 74276

African (AFR) AF: 0.759 AC: 31433 AN: 41420

American (AMR) AF: 0.840 AC: 12828 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2834 AN: 3472

East Asian (EAS) AF: 0.458 AC: 2359 AN: 5148

South Asian (SAS) AF: 0.725 AC: 3485 AN: 4808

European-Finnish (FIN) AF: 0.851 AC: 8968 AN: 10536

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56931 AN: 67982

Other (OTH) AF: 0.780 AC: 1646 AN: 2110

Alfa AF: 0.824 Hom.: 6431

Bravo AF: 0.797

Asia WGS AF: 0.650 AC: 2261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.30
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs1121401; hg19: chr12-9136622;