rs9318225

chr13-73917128-T-Cchr13-73917128-T-G

Variant summary

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

The ENST00000377669.7(KLF12):c.123+26853A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,080 control chromosomes in the GnomAD database, including 9,006 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 0.33 (9006 hom., cov: 32)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF12	NM_001400136.1	c.123+26853A>G		intron_variant		ENST00000703967.1
KLF12	NM_001400153.1	c.123+26853A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF12	ENST00000703967.1	c.123+26853A>G		intron_variant			NM_001400136.1	P1
KLF12	ENST00000377669.7	c.123+26853A>G		intron_variant		1		P1
KLF12	ENST00000472022.1	n.157+26853A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50301 AN: 151960 Hom.: 8991 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.331 AC: 50342 AN: 152080 Hom.: 9006 Cov.: 32 AF XY: 0.337 AC XY: 25063 AN XY: 74340

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.292

Alfa AF: 0.308 Hom.: 10656

Bravo AF: 0.333

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.43
Dann	Benign	0.77

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

Other links and lift over

dbSNP: rs9318225; hg19: chr13-74491265;