chr12-8986301-G-A

Variant names:

• chr12-8986301-G-A
• rs10842660
• NM_001329101.2:c.-155-5905G>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.-155-5905G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,998 control chromosomes in the GnomAD database, including 10,606 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 0.35 (10606 hom., cov: 31)
• Consequence: KLRG1 NM_001329101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 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.-155-5905G>A		intron	N/A	NP_001316030.1
	KLRG1	NM_001329102.2		c.-289-3911G>A		intron	N/A	NP_001316031.1
	KLRG1	NM_001329103.2		c.-155-5905G>A		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.-155-5905G>A		intron	N/A	ENSP00000445627.1
	KLRG1	ENST00000538029.1	TSL:2	n.113-22674G>A		intron	N/A
	KLRG1	ENST00000541957.1	TSL:4	n.248-3911G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52886 AN: 151878 Hom.: 10602 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.348 AC: 52901 AN: 151998 Hom.: 10606 Cov.: 31 AF XY: 0.351 AC XY: 26063 AN XY: 74280

African (AFR) AF: 0.136 AC: 5649 AN: 41474

American (AMR) AF: 0.369 AC: 5629 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2056 AN: 5166

South Asian (SAS) AF: 0.440 AC: 2119 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4973 AN: 10544

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29684 AN: 67940

Other (OTH) AF: 0.366 AC: 773 AN: 2112

Alfa AF: 0.341 Hom.: 1513

Bravo AF: 0.332

Asia WGS AF: 0.408 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.25
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs10842660; hg19: chr12-9138897;