12-9001336-G-A

Variant names:

• chr12-9001336-G-A
• rs11048434
• NM_005810.4:c.357+6048G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005810.4. 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_005810.4	MANE Select	c.357+6048G>A		intron	N/A	NP_005801.3
	KLRG1	NM_001329099.2		c.357+6048G>A		intron	N/A	NP_001316028.1
	KLRG1	NM_001329101.2		c.120+6048G>A		intron	N/A	NP_001316030.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	ENST00000356986.8	TSL:1 MANE Select	c.357+6048G>A		intron	N/A	ENSP00000349477.3
	KLRG1	ENST00000266551.8	TSL:1	c.357+6048G>A		intron	N/A	ENSP00000266551.4
	KLRG1	ENST00000539240.5	TSL:3	c.120+6048G>A		intron	N/A	ENSP00000445627.1

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

African (AFR) AF: 0.105 AC: 4338 AN: 41468

American (AMR) AF: 0.331 AC: 5049 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3468

East Asian (EAS) AF: 0.399 AC: 2055 AN: 5154

South Asian (SAS) AF: 0.384 AC: 1848 AN: 4814

European-Finnish (FIN) AF: 0.385 AC: 4066 AN: 10548

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24219 AN: 67994

Other (OTH) AF: 0.305 AC: 645 AN: 2114

Alfa AF: 0.341 Hom.: 41567

Bravo AF: 0.277

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.59
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11048434; hg19: chr12-9153932;