rs1805721

Positions:

• chr12-8994973-G-A
• chr12-8994973-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLRG1	NM_005810.4	c.188-146G>A		intron_variant		ENST00000356986.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRG1	ENST00000356986.8	c.188-146G>A		intron_variant		1	NM_005810.4	P1
	ENST00000545706.1	n.70+1524C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.426

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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.366

Alfa AF: 0.394 Hom.: 6546

Bravo AF: 0.332

Asia WGS AF: 0.406 AC: 1416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.56

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: rs1805721; hg19: chr12-9147569;