rs10842660

Positions:

• chr12-8986301-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRG1	NM_001329101.2	c.-155-5905G>A		intron_variant			NP_001316030.1
KLRG1	NM_001329102.2	c.-289-3911G>A		intron_variant			NP_001316031.1
KLRG1	NM_001329103.2	c.-155-5905G>A		intron_variant			NP_001316032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG1	ENST00000539240.5	c.-155-5905G>A		intron_variant		3		ENSP00000445627
KLRG1	ENST00000538029.1	n.113-22674G>A		intron_variant, non_coding_transcript_variant		2
KLRG1	ENST00000541957.1	n.248-3911G>A		intron_variant, non_coding_transcript_variant		4
KLRG1	ENST00000544226.5	n.131-5905G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.366

Alfa AF: 0.348 Hom.: 1506

Bravo AF: 0.332

Asia WGS AF: 0.408 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10842660; hg19: chr12-9138897;