Variant 13-73764967-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007249.5(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
NM_007249.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.333

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 made for transcript

Verdict is Benign. Variant got -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/exons	Protein
KLF12	NM_001400136.1 linkuse as main transcript	c.840C>A	p.Gly280Gly	synonymous_variant	6/8	NP_001387065.1
KLF12	NM_001400139.1 linkuse as main transcript	c.840C>A	p.Gly280Gly	synonymous_variant	6/8	NP_001387068.1
KLF12	NM_001400141.1 linkuse as main transcript	c.840C>A	p.Gly280Gly	synonymous_variant	6/8	NP_001387070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7 linkuse as main transcript	c.840C>A	p.Gly280Gly	synonymous_variant	6/8	1		ENSP00000366897.2		Q9Y4X4-1
KLF12	ENST00000703967.1 linkuse as main transcript	c.840C>A	p.Gly280Gly	synonymous_variant	6/8			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

GnomAD3 exomes

AF:

0.483

AC:

118530

AN:

245636

Hom.:

30630

AF XY:

0.497

AC XY:

66051

AN XY:

132994

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 SAS exome

AF:

0.579

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

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.582

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.559

Gnomad4 OTH exome

AF:

0.529

GnomAD4 genome

AF:

0.481

AC:

73005

AN:

151874

Hom.:

18278

Cov.:

AF XY:

0.475

AC XY:

35264

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.402

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.556

Gnomad4 OTH

AF:

0.494

Alfa

AF:

0.543

Hom.:

25807

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

DANN

Benign

0.71

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over