chr12-9010581-A-G

Position:

• chr12-9010581-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005810.4(KLRG1):​c.*1044A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,158 control chromosomes in the GnomAD database, including 4,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4860 hom., cov: 32)
  • Exomes 𝑓: 0.23 (3 hom.)
• Consequence: KLRG1 NM_005810.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.120

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]

KLRG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-9010581-A-G is Benign according to our data. Variant chr12-9010581-A-G is described in ClinVar as [Benign]. Clinvar id is 1279791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRG1	NM_005810.4	c.*1044A>G		3_prime_UTR_variant	5/5	ENST00000356986.8	NP_005801.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG1	ENST00000356986.8	c.*1044A>G		3_prime_UTR_variant	5/5	1	NM_005810.4	ENSP00000349477.3
KLRG1	ENST00000266551.8	c.*553A>G		3_prime_UTR_variant	6/6	1		ENSP00000266551.4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35419 AN: 151930 Hom.: 4855 Cov.: 32

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.227 AC: 25 AN: 110 Hom.: 3 Cov.: 0 AF XY: 0.212 AC XY: 14 AN XY: 66

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.333

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.233 AC: 35432 AN: 152048 Hom.: 4860 Cov.: 32 AF XY: 0.233 AC XY: 17326 AN XY: 74320

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.267

Alfa AF: 0.277 Hom.: 4850

Bravo AF: 0.232

Asia WGS AF: 0.348 AC: 1207 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 27424220) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1805672; hg19: chr12-9163177;