13-74061451-G-T

Variant names:

• chr13-74061451-G-T
• rs1324913
• NM_001400136.1:c.-31-66398C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001400136.1(KLF12):​c.-31-66398C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,792 control chromosomes in the GnomAD database, including 12,158 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 0.39 (12158 hom., cov: 31)
• Consequence: KLF12 NM_001400136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.-31-66398C>A		intron_variant	Intron 1 of 7	ENST00000703967.1	NP_001387065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000703967.1	c.-31-66398C>A		intron_variant	Intron 1 of 7		NM_001400136.1	ENSP00000515592.1
KLF12	ENST00000377669.7	c.-31-66398C>A		intron_variant	Intron 1 of 7	1		ENSP00000366897.2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58534 AN: 151674 Hom.: 12127 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.386 AC: 58623 AN: 151792 Hom.: 12158 Cov.: 31 AF XY: 0.382 AC XY: 28338 AN XY: 74174

African (AFR) AF: 0.525 AC: 21738 AN: 41392

American (AMR) AF: 0.437 AC: 6676 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3460

East Asian (EAS) AF: 0.126 AC: 652 AN: 5166

South Asian (SAS) AF: 0.198 AC: 950 AN: 4802

European-Finnish (FIN) AF: 0.309 AC: 3246 AN: 10506

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22930 AN: 67886

Other (OTH) AF: 0.378 AC: 798 AN: 2110

Alfa AF: 0.346 Hom.: 27505

Bravo AF: 0.404

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.062
DANN	Benign	0.55
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1324913; hg19: chr13-74635588;