Genetic Variant NM_001329101.2:c.-156+416G>T (chr12-8950652-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001329101.2(KLRG1):c.-156+416G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,718 control chromosomes in the GnomAD database, including 38,375 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 0.69 ( 38375 hom., cov: 29)

Consequence

KLRG1
NM_001329101.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.523

Publications

7 publications found

Variant links:

Genes affected

M6PR (HGNC:6752): (mannose-6-phosphate receptor, cation dependent) This gene encodes a member of the P-type lectin family. P-type lectins play a critical role in lysosome function through the specific transport of mannose-6-phosphate-containing acid hydrolases from the Golgi complex to lysosomes. The encoded protein functions as a homodimer and requires divalent cations for ligand binding. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome X. [provided by RefSeq, May 2011]

M6PR links:

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329101.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
KLRG1	NM_001329101.2	c.-156+416G>T	intron	N/A	NP_001316030.1
KLRG1	NM_001329102.2	c.-290+416G>T	intron	N/A	NP_001316031.1
KLRG1	NM_001329103.2	c.-156+467G>T	intron	N/A	NP_001316032.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
M6PR	ENST00000891555.1		c.-2+480C>A	intron	N/A	ENSP00000561614.1
M6PR	ENST00000941063.1		c.-2+1140C>A	intron	N/A	ENSP00000611122.1
KLRG1	ENST00000539240.5	TSL:3	c.-156+416G>T	intron	N/A	ENSP00000445627.1	F5H207

Frequencies

GnomAD3 genomes

AF:

0.694

AC:

105139

AN:

151600

Hom.:

38353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.774

Gnomad ASJ

AF:

0.774

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.805

Gnomad OTH

AF:

0.682

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.693

AC:

105207

AN:

151718

Hom.:

38375

Cov.:

AF XY:

0.693

AC XY:

51361

AN XY:

74136

show subpopulations

African (AFR)

AF:

0.462

AC:

19062

AN:

41242

American (AMR)

AF:

0.775

AC:

11815

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.774

AC:

2687

AN:

3470

East Asian (EAS)

AF:

0.452

AC:

2322

AN:

5132

South Asian (SAS)

AF:

0.734

AC:

3528

AN:

4806

European-Finnish (FIN)

AF:

0.825

AC:

8704

AN:

10548

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.805

AC:

54728

AN:

67962

Other (OTH)

AF:

0.684

AC:

1440

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1431

2862

4294

5725

7156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.676

Hom.:

2474

Bravo

AF:

0.678

Asia WGS

AF:

0.633

AC:

2202

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

1.3

(source)

DANN

Benign

0.47

PhyloP100

-0.52

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over