rs1805723

chr12-8989701-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005810.4(KLRG1):c.66T>C(p.Tyr22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,599,442 control chromosomes in the GnomAD database, including 155,614 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 0.36 (10908 hom., cov: 33)
  • Exomes 𝑓: 0.44 (144706 hom.)
• Consequence: KLRG1 NM_005810.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-0.457 with no splicing effect.
• 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.66T>C	p.Tyr22=	synonymous_variant	1/5	ENST00000356986.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRG1	ENST00000356986.8	c.66T>C	p.Tyr22=	synonymous_variant	1/5	1	NM_005810.4	P1
	ENST00000545706.1	n.71-1271A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54634 AN: 152000 Hom.: 10899 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.374

GnomAD3 exomes AF: 0.425 AC: 105128 AN: 247492 Hom.: 23151 AF XY: 0.429 AC XY: 57410 AN XY: 133948

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.475

Gnomad EAS exome AF: 0.383

Gnomad SAS exome AF: 0.429

Gnomad FIN exome AF: 0.473

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.443 AC: 641219 AN: 1447324 Hom.: 144706 Cov.: 28 AF XY: 0.443 AC XY: 318972 AN XY: 720774

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.451

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.359 AC: 54674 AN: 152118 Hom.: 10908 Cov.: 33 AF XY: 0.361 AC XY: 26869 AN XY: 74336

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.378

Alfa AF: 0.422 Hom.: 14024

Bravo AF: 0.346

Asia WGS AF: 0.414 AC: 1443 AN: 3478

EpiCase AF: 0.433

EpiControl AF: 0.439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.2
Dann	Benign	0.62

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: rs1805723; hg19: chr12-9142297; COSMIC: COSV56942161; COSMIC: COSV56942161;