rs9600235

Positions:

• chr13-74130150-C-T

Variant summary

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

The NM_007249.5(KLF12):​c.-32+3589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,148 control chromosomes in the GnomAD database, including 2,181 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 0.16 (2181 hom., cov: 32)
• Consequence: KLF12 NM_007249.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.-32+3822G>A		intron_variant			NP_001387065.1
KLF12	NM_001400139.1	c.-31-135097G>A		intron_variant			NP_001387068.1
KLF12	NM_007249.5	c.-32+3589G>A		intron_variant			NP_009180.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7	c.-32+3589G>A		intron_variant		1		ENSP00000366897.2
KLF12	ENST00000703967.1	c.-32+3822G>A		intron_variant				ENSP00000515592.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24882 AN: 152030 Hom.: 2164 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.164 AC: 24944 AN: 152148 Hom.: 2181 Cov.: 32 AF XY: 0.164 AC XY: 12230 AN XY: 74364

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0591

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.176

Alfa AF: 0.153 Hom.: 3786

Bravo AF: 0.163

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9600235; hg19: chr13-74704287;