dbSNP rs1805672: KLRG1:c.*1044A>G (chr12-9010581-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.120

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
KLRG1	NM_005810.4 link	c.*1044A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000356986.8	NP_005801.3	Q96E93-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRG1	ENST00000356986.8 link	c.*1044A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_005810.4	ENSP00000349477.3		Q96E93-2
KLRG1	ENST00000266551.8 link	c.*553A>G		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000266551.4		Q96E93-1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35419

AN:

151930

Hom.:

4855

Cov.:

show subpopulations

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:

AN:

110

Hom.:

Cov.:

AF XY:

0.212

AC XY:

AN XY:

show subpopulations

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.:

AF XY:

0.233

AC XY:

17326

AN XY:

74320

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over