NM_001400136.1:c.-32+3822G>A

Variant names:

• chr13-74130150-C-T
• rs9600235
• NM_001400136.1:c.-32+3822G>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.-32+3822G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,148 control chromosomes in the GnomAD database, including 2,181 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 0.16 (2181 hom., cov: 32)
• Consequence: KLF12 NM_001400136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 8 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	NM_001400136.1	MANE Select	c.-32+3822G>A		intron	N/A	NP_001387065.1
	KLF12	NM_001400139.1		c.-31-135097G>A		intron	N/A	NP_001387068.1
	KLF12	NM_007249.5		c.-32+3589G>A		intron	N/A	NP_009180.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	ENST00000703967.1	MANE Select	c.-32+3822G>A		intron	N/A	ENSP00000515592.1
	KLF12	ENST00000377669.7	TSL:1	c.-32+3589G>A		intron	N/A	ENSP00000366897.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24882 AN: 152030 Hom.: 2164 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.164 AC: 24944 AN: 152148 Hom.: 2181 Cov.: 32 AF XY: 0.164 AC XY: 12230 AN XY: 74364

African (AFR) AF: 0.207 AC: 8576 AN: 41484

American (AMR) AF: 0.145 AC: 2222 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3466

East Asian (EAS) AF: 0.0591 AC: 307 AN: 5192

South Asian (SAS) AF: 0.181 AC: 872 AN: 4812

European-Finnish (FIN) AF: 0.149 AC: 1570 AN: 10568

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10252 AN: 68016

Other (OTH) AF: 0.176 AC: 372 AN: 2114

Alfa AF: 0.153 Hom.: 7792

Bravo AF: 0.163

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.75
PhyloP100		0.37
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: rs9600235; hg19: chr13-74704287;