13-73859670-T-G

Position:

• chr13-73859670-T-G

Variant summary

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

The NM_007249.5(KLF12):​c.124-13297A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,026 control chromosomes in the GnomAD database, including 34,634 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 0.67 (34634 hom., cov: 32)
• Consequence: KLF12 NM_007249.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.124-13297A>C		intron_variant			NP_001387065.1
KLF12	NM_001400139.1	c.124-13297A>C		intron_variant			NP_001387068.1
KLF12	NM_001400141.1	c.124-13297A>C		intron_variant			NP_001387070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7	c.124-13297A>C		intron_variant		1		ENSP00000366897.2
KLF12	ENST00000703967.1	c.124-13297A>C		intron_variant				ENSP00000515592.1
KLF12	ENST00000472022.1	n.158-13297A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101521 AN: 151908 Hom.: 34616 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.668 AC: 101581 AN: 152026 Hom.: 34634 Cov.: 32 AF XY: 0.671 AC XY: 49873 AN XY: 74302

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.646

Alfa AF: 0.712 Hom.: 42630

Bravo AF: 0.654

Asia WGS AF: 0.650 AC: 2256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.25
DANN	Benign	0.78

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: rs4883955; hg19: chr13-74433807;