12-8994973-G-A

Variant names:

• chr12-8994973-G-A
• rs1805721
• NM_005810.4:c.188-146G>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.188-146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 587,290 control chromosomes in the GnomAD database, including 53,786 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 (10611 hom., cov: 32)
  • Exomes 𝑓: 0.44 (43175 hom.)
• Consequence: KLRG1 NM_005810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726
• Publications: 17 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]

ENSG00000257105 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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_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.188-146G>A		intron	N/A	NP_005801.3
	KLRG1	NM_001329099.2		c.188-146G>A		intron	N/A	NP_001316028.1
	KLRG1	NM_001329101.2		c.-50-146G>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.188-146G>A		intron	N/A	ENSP00000349477.3
	KLRG1	ENST00000266551.8	TSL:1	c.188-146G>A		intron	N/A	ENSP00000266551.4
	KLRG1	ENST00000539240.5	TSL:3	c.-50-146G>A		intron	N/A	ENSP00000445627.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52920 AN: 152010 Hom.: 10606 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.439 AC: 191013 AN: 435162 Hom.: 43175 AF XY: 0.438 AC XY: 98298 AN XY: 224416

African (AFR) AF: 0.137 AC: 1495 AN: 10894

American (AMR) AF: 0.413 AC: 4816 AN: 11666

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 5893 AN: 12380

East Asian (EAS) AF: 0.453 AC: 12273 AN: 27120

South Asian (SAS) AF: 0.428 AC: 12011 AN: 28070

European-Finnish (FIN) AF: 0.467 AC: 16069 AN: 34388

Middle Eastern (MID) AF: 0.430 AC: 836 AN: 1942

European-Non Finnish (NFE) AF: 0.448 AC: 127175 AN: 284172

Other (OTH) AF: 0.426 AC: 10445 AN: 24530

GnomAD4 genome AF: 0.348 AC: 52937 AN: 152128 Hom.: 10611 Cov.: 32 AF XY: 0.351 AC XY: 26077 AN XY: 74360

African (AFR) AF: 0.137 AC: 5669 AN: 41506

American (AMR) AF: 0.368 AC: 5624 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2055 AN: 5164

South Asian (SAS) AF: 0.438 AC: 2111 AN: 4820

European-Finnish (FIN) AF: 0.471 AC: 4974 AN: 10570

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29687 AN: 67986

Other (OTH) AF: 0.366 AC: 772 AN: 2110

Alfa AF: 0.395 Hom.: 9316

Bravo AF: 0.332

Asia WGS AF: 0.406 AC: 1416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		-0.73
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: rs1805721; hg19: chr12-9147569;