chr12-9000661-C-T

Variant names:

• chr12-9000661-C-T
• rs10400563
• NM_005810.4:c.357+5373C>T

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+5373C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,080 control chromosomes in the GnomAD database, including 37,641 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 0.70 (37641 hom., cov: 32)
• Consequence: KLRG1 NM_005810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• Publications: 8 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 (AMR) allele frequency at 95% confidence interval = 0.745 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	NM_005810.4	MANE Select	c.357+5373C>T		intron	N/A	NP_005801.3
	KLRG1	NM_001329099.2		c.357+5373C>T		intron	N/A	NP_001316028.1	Q96E93-1
	KLRG1	NM_001329101.2		c.120+5373C>T		intron	N/A	NP_001316030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	ENST00000356986.8	TSL:1 MANE Select	c.357+5373C>T		intron	N/A	ENSP00000349477.3	Q96E93-2
	KLRG1	ENST00000266551.8	TSL:1	c.357+5373C>T		intron	N/A	ENSP00000266551.4	Q96E93-1
	KLRG1	ENST00000539240.5	TSL:3	c.120+5373C>T		intron	N/A	ENSP00000445627.1	F5H207

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106128 AN: 151962 Hom.: 37605 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.698 AC: 106224 AN: 152080 Hom.: 37641 Cov.: 32 AF XY: 0.697 AC XY: 51804 AN XY: 74350

African (AFR) AF: 0.610 AC: 25289 AN: 41464

American (AMR) AF: 0.753 AC: 11499 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2334 AN: 3472

East Asian (EAS) AF: 0.457 AC: 2362 AN: 5168

South Asian (SAS) AF: 0.643 AC: 3104 AN: 4824

European-Finnish (FIN) AF: 0.792 AC: 8372 AN: 10568

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51028 AN: 67982

Other (OTH) AF: 0.678 AC: 1435 AN: 2116

Alfa AF: 0.731 Hom.: 52672

Bravo AF: 0.693

Asia WGS AF: 0.618 AC: 2151 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	0.66
DANN	Benign	0.16
PhyloP100		-0.95
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: rs10400563; hg19: chr12-9153257;