rs9543524

chr13-74084367-T-G

Variant summary

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

The ENST00000377669.7(KLF12):c.-32+49372A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,076 control chromosomes in the GnomAD database, including 2,999 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 0.19 (2999 hom., cov: 32)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF12	NM_001400136.1	c.-32+49605A>C		intron_variant		ENST00000703967.1
KLF12	NM_001400153.1	c.-31-89314A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF12	ENST00000703967.1	c.-32+49605A>C		intron_variant			NM_001400136.1	P1
KLF12	ENST00000377669.7	c.-32+49372A>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29383 AN: 151956 Hom.: 2994 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.193 AC: 29411 AN: 152076 Hom.: 2999 Cov.: 32 AF XY: 0.189 AC XY: 14067 AN XY: 74372

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.0517

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.185

Alfa AF: 0.189 Hom.: 341

Bravo AF: 0.195

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.72
Dann	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9543524; hg19: chr13-74658504;