13-73862019-T-C

Position:

• chr13-73862019-T-C

Variant summary

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

The NM_007249.5(KLF12):​c.124-15646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,110 control chromosomes in the GnomAD database, including 18,431 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 0.49 (18431 hom., cov: 30)
• Consequence: KLF12 NM_007249.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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]

KLF12 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.124-15646A>G		intron_variant			NP_001387065.1
KLF12	NM_001400139.1	c.124-15646A>G		intron_variant			NP_001387068.1
KLF12	NM_001400141.1	c.124-15646A>G		intron_variant			NP_001387070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7	c.124-15646A>G		intron_variant		1		ENSP00000366897.2
KLF12	ENST00000703967.1	c.124-15646A>G		intron_variant				ENSP00000515592.1
KLF12	ENST00000472022.1	n.158-15646A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73338 AN: 151002 Hom.: 18437 Cov.: 30

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.485 AC: 73336 AN: 151110 Hom.: 18431 Cov.: 30 AF XY: 0.479 AC XY: 35331 AN XY: 73752

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.496

Alfa AF: 0.534 Hom.: 30317

Bravo AF: 0.479

Asia WGS AF: 0.302 AC: 1058 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.70

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: rs3764109; hg19: chr13-74436156; COSMIC: COSV66580481;