Genetic Variant ENST00000377669.7:c.840C>A (chr13-73764967-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The ENST00000377669.7(KLF12):c.840C>A(p.Gly280Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,550,362 control chromosomes in the GnomAD database, including 225,591 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 0.48 ( 18278 hom., cov: 31)

Exomes 𝑓: 0.53 ( 207313 hom. )

Consequence

KLF12
ENST00000377669.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.333

Publications

16 publications found

Variant links:

Genes affected

KLF12 (HGNC:6346): (KLF transcription factor 12) Activator protein-2 alpha (AP-2 alpha) is a developmentally-regulated transcription factor and important regulator of gene expression during vertebrate development and carcinogenesis. The protein encoded by this gene is a member of the Kruppel-like zinc finger protein family and can repress expression of the AP-2 alpha gene by binding to a specific site in the AP-2 alpha gene promoter. Repression by the encoded protein requires binding with a corepressor, CtBP1. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KLF12 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=-0.53).

BP7

Synonymous conserved (PhyloP=0.333 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
KLF12	NM_001400136.1 link	c.840C>A	p.Gly280Gly	synonymous_variant	Exon 6 of 8	NP_001387065.1
KLF12	NM_001400139.1 link	c.840C>A	p.Gly280Gly	synonymous_variant	Exon 6 of 8	NP_001387068.1
KLF12	NM_001400141.1 link	c.840C>A	p.Gly280Gly	synonymous_variant	Exon 6 of 8	NP_001387070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7 link	c.840C>A	p.Gly280Gly	synonymous_variant	Exon 6 of 8	1		ENSP00000366897.2		Q9Y4X4-1
KLF12	ENST00000703967.1 link	c.840C>A	p.Gly280Gly	synonymous_variant	Exon 6 of 8			ENSP00000515592.1		Q9Y4X4-1

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

72964

AN:

151756

Hom.:

18268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.729

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.483

AC:

118530

AN:

245636

AF XY:

0.497

show subpopulations

Gnomad AFR exome

AF:

0.391

Gnomad AMR exome

AF:

0.355

Gnomad ASJ exome

AF:

0.616

Gnomad EAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.552

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.535

AC:

748115

AN:

1398488

Hom.:

207313

Cov.:

AF XY:

0.538

AC XY:

376289

AN XY:

699048

show subpopulations

African (AFR)

AF:

0.382

AC:

12336

AN:

32326

American (AMR)

AF:

0.360

AC:

15857

AN:

44032

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

15493

AN:

25520

East Asian (EAS)

AF:

0.194

AC:

7656

AN:

39514

South Asian (SAS)

AF:

0.582

AC:

49011

AN:

84152

European-Finnish (FIN)

AF:

0.444

AC:

23617

AN:

53166

Middle Eastern (MID)

AF:

0.554

AC:

3127

AN:

5640

European-Non Finnish (NFE)

AF:

0.559

AC:

590199

AN:

1055928

Other (OTH)

AF:

0.529

AC:

30819

AN:

58210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

14537

29074

43612

58149

72686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15922

31844

47766

63688

79610

<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:

0.481

AC:

73005

AN:

151874

Hom.:

18278

Cov.:

AF XY:

0.475

AC XY:

35264

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.402

AC:

16621

AN:

41376

American (AMR)

AF:

0.406

AC:

6192

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

2125

AN:

3472

East Asian (EAS)

AF:

0.198

AC:

1020

AN:

5152

South Asian (SAS)

AF:

0.570

AC:

2740

AN:

4808

European-Finnish (FIN)

AF:

0.439

AC:

4619

AN:

10526

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.556

AC:

37809

AN:

67970

Other (OTH)

AF:

0.494

AC:

1043

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1878

3757

5635

7514

9392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.525

Hom.:

41690

Bravo

AF:

0.473

Asia WGS

AF:

0.384

AC:

1332

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.4

(source)

DANN

Benign

0.71

PhyloP100

0.33

Mutation Taster

=100/0

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