rs11048434

Positions:

• chr12-9001336-G-A
• chr12-9001336-G-T

Variant summary

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

The NM_005810.4(KLRG1):​c.357+6048G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,034 control chromosomes in the GnomAD database, including 7,404 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 0.29 (7404 hom., cov: 32)
• Consequence: KLRG1 NM_005810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRG1	NM_005810.4	c.357+6048G>A		intron_variant		ENST00000356986.8	NP_005801.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG1	ENST00000356986.8	c.357+6048G>A		intron_variant		1	NM_005810.4	ENSP00000349477	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43850 AN: 151916 Hom.: 7397 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.289 AC: 43878 AN: 152034 Hom.: 7404 Cov.: 32 AF XY: 0.293 AC XY: 21740 AN XY: 74312

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.305

Alfa AF: 0.352 Hom.: 19648

Bravo AF: 0.277

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11048434; hg19: chr12-9153932;