rs6650443

chr13-73713812-G-Achr13-73713812-G-C

Variant summary

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

The ENST00000377669.7(KLF12):c.1027+1556C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,172 control chromosomes in the GnomAD database, including 42,764 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 0.75 (42764 hom., cov: 32)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF12	NM_001400136.1	c.1027+1556C>T		intron_variant		ENST00000703967.1
KLF12	NM_001400153.1	c.870-18141C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF12	ENST00000703967.1	c.1027+1556C>T		intron_variant			NM_001400136.1	P1
KLF12	ENST00000377669.7	c.1027+1556C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113839 AN: 152054 Hom.: 42740 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.749 AC: 113907 AN: 152172 Hom.: 42764 Cov.: 32 AF XY: 0.746 AC XY: 55466 AN XY: 74384

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.760

Alfa AF: 0.755 Hom.: 6347

Bravo AF: 0.746

Asia WGS AF: 0.760 AC: 2640 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.5
Dann	Benign	0.45

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: rs6650443; hg19: chr13-74287949;