rs9543524

Variant names:

• chr13-74084367-T-G
• rs9543524
• NM_001400136.1:c.-32+49605A>C

Variant summary

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

The NM_001400136.1(KLF12):​c.-32+49605A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,076 control chromosomes in the GnomAD database, including 2,999 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 0.19 (2999 hom., cov: 32)
• Consequence: KLF12 NM_001400136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400136.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	NM_001400136.1	MANE Select	c.-32+49605A>C		intron	N/A	NP_001387065.1
	KLF12	NM_001400139.1		c.-31-89314A>C		intron	N/A	NP_001387068.1
	KLF12	NM_007249.5		c.-32+49372A>C		intron	N/A	NP_009180.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	ENST00000703967.1	MANE Select	c.-32+49605A>C		intron	N/A	ENSP00000515592.1
	KLF12	ENST00000377669.7	TSL:1	c.-32+49372A>C		intron	N/A	ENSP00000366897.2
	KLF12	ENST00000885983.1		c.-32+49605A>C		intron	N/A	ENSP00000556042.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29383 AN: 151956 Hom.: 2994 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.193 AC: 29411 AN: 152076 Hom.: 2999 Cov.: 32 AF XY: 0.189 AC XY: 14067 AN XY: 74372

African (AFR) AF: 0.272 AC: 11259 AN: 41450

American (AMR) AF: 0.141 AC: 2155 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3470

East Asian (EAS) AF: 0.0517 AC: 268 AN: 5182

South Asian (SAS) AF: 0.137 AC: 662 AN: 4816

European-Finnish (FIN) AF: 0.128 AC: 1356 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12539 AN: 67976

Other (OTH) AF: 0.185 AC: 388 AN: 2100

Alfa AF: 0.194 Hom.: 375

Bravo AF: 0.195

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.48
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: rs9543524; hg19: chr13-74658504;