rs9543532

Variant names:

• chr13-74127245-T-C
• rs9543532
• ENST00000377669.7:c.-32+6494A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007249.5(KLF12):​c.-32+6494A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,160 control chromosomes in the GnomAD database, including 27,557 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 0.54 (27557 hom., cov: 33)
• Consequence: KLF12 NM_007249.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.-32+6727A>G		intron_variant	Intron 1 of 7		NP_001387065.1
KLF12	NM_001400139.1	c.-31-132192A>G		intron_variant	Intron 1 of 7		NP_001387068.1
KLF12	NM_007249.5	c.-32+6494A>G		intron_variant	Intron 1 of 7		NP_009180.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7	c.-32+6494A>G		intron_variant	Intron 1 of 7	1		ENSP00000366897.2
KLF12	ENST00000703967.1	c.-32+6727A>G		intron_variant	Intron 1 of 7			ENSP00000515592.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82706 AN: 152042 Hom.: 27559 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.544 AC: 82708 AN: 152160 Hom.: 27557 Cov.: 33 AF XY: 0.546 AC XY: 40589 AN XY: 74382

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.556

Alfa AF: 0.613 Hom.: 3992

Bravo AF: 0.527

Asia WGS AF: 0.624 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9543532; hg19: chr13-74701382;