rs7333671

Positions:

• chr13-73704828-A-G

Variant summary

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

The ENST00000377669.7(KLF12):​c.1028-9157T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,136 control chromosomes in the GnomAD database, including 1,312 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 0.12 (1312 hom., cov: 32)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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 (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF12	NM_001400136.1	c.1028-9157T>C		intron_variant		ENST00000703967.1
KLF12	NM_001400153.1	c.870-9157T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF12	ENST00000703967.1	c.1028-9157T>C		intron_variant			NM_001400136.1	P1
KLF12	ENST00000377669.7	c.1028-9157T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17731 AN: 152018 Hom.: 1309 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0255

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.117 AC: 17762 AN: 152136 Hom.: 1312 Cov.: 32 AF XY: 0.114 AC XY: 8479 AN XY: 74382

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.0255

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0950 Hom.: 1084

Bravo AF: 0.120

Asia WGS AF: 0.121 AC: 422 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	0.61
DANN	Benign	0.31

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: rs7333671; hg19: chr13-74278965;