Genetic Variant NM_005810.4:c.66T>C (chr12-8989701-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005810.4(KLRG1):c.66T>C(p.Tyr22Tyr) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.457

Publications

25 publications found

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:

ENSG00000257105 (HGNC:):

ENSG00000257105 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KLRG1	NM_005810.4 link	c.66T>C	p.Tyr22Tyr	synonymous_variant	Exon 1 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.66T>C	p.Tyr22Tyr	synonymous_variant	Exon 1 of 5	1	NM_005810.4	ENSP00000349477.3		Q96E93-2

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54634

AN:

152000

Hom.:

10899

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.425

AC:

105128

AN:

247492

AF XY:

0.429

show subpopulations

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 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.:

AF XY:

0.443

AC XY:

318972

AN XY:

720774

show subpopulations

African (AFR)

AF:

0.163

AC:

5427

AN:

33228

American (AMR)

AF:

0.447

AC:

19555

AN:

43788

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

12411

AN:

25994

East Asian (EAS)

AF:

0.438

AC:

17312

AN:

39508

South Asian (SAS)

AF:

0.431

AC:

36885

AN:

85552

European-Finnish (FIN)

AF:

0.469

AC:

24930

AN:

53152

Middle Eastern (MID)

AF:

0.410

AC:

2354

AN:

5742

European-Non Finnish (NFE)

AF:

0.451

AC:

496356

AN:

1100474

Other (OTH)

AF:

0.434

AC:

25989

AN:

59886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

14649

29297

43946

58594

73243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14898

29796

44694

59592

74490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.359

AC:

54674

AN:

152118

Hom.:

10908

Cov.:

AF XY:

0.361

AC XY:

26869

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.175

AC:

7269

AN:

41512

American (AMR)

AF:

0.373

AC:

5694

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

1638

AN:

3472

East Asian (EAS)

AF:

0.399

AC:

2062

AN:

5172

South Asian (SAS)

AF:

0.439

AC:

2117

AN:

4820

European-Finnish (FIN)

AF:

0.471

AC:

4972

AN:

10560

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29719

AN:

67994

Other (OTH)

AF:

0.378

AC:

797

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1695

3391

5086

6782

8477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.415

Hom.:

19474

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

(source)

DANN

Benign

0.62

PhyloP100

-0.46

PromoterAI

0.092

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over