rs12429889

Variant names:

• chr13-74168185-T-C
• rs12429889
• XM_011534909.3:c.-68A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011534909.3(KLF12):​c.-68A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,198 control chromosomes in the GnomAD database, including 9,523 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 0.28 (9523 hom., cov: 32)
• Consequence: KLF12 XM_011534909.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF12	XM_011534909.3	c.-68A>G		5_prime_UTR_variant	Exon 1 of 8		XP_011533211.1
KLF12	NM_001400139.1	c.-32+137811A>G		intron_variant	Intron 1 of 7		NP_001387068.1
KLF12	NM_001400153.1	c.-32+137811A>G		intron_variant	Intron 1 of 6		NP_001387082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42595 AN: 152080 Hom.: 9495 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.280 AC: 42673 AN: 152198 Hom.: 9523 Cov.: 32 AF XY: 0.275 AC XY: 20475 AN XY: 74422

African (AFR) AF: 0.620 AC: 25738 AN: 41482

American (AMR) AF: 0.204 AC: 3123 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3468

East Asian (EAS) AF: 0.140 AC: 728 AN: 5184

South Asian (SAS) AF: 0.230 AC: 1112 AN: 4830

European-Finnish (FIN) AF: 0.0749 AC: 795 AN: 10616

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9494 AN: 68004

Other (OTH) AF: 0.271 AC: 572 AN: 2112

Alfa AF: 0.192 Hom.: 9561

Bravo AF: 0.300

Asia WGS AF: 0.243 AC: 846 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.34
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs12429889; hg19: chr13-74742322;