chr13-74065662-T-C

Variant names:

• chr13-74065662-T-C
• rs9565072
• NM_001400136.1:c.-32+68310A>G

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+68310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,826 control chromosomes in the GnomAD database, including 25,812 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 0.55 (25812 hom., cov: 29)
• Consequence: KLF12 NM_001400136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 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+68310A>G		intron	N/A	NP_001387065.1	Q9Y4X4-1
	KLF12	NM_001400139.1		c.-31-70609A>G		intron	N/A	NP_001387068.1	Q9Y4X4-1
	KLF12	NM_007249.5		c.-32+68077A>G		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+68310A>G		intron	N/A	ENSP00000515592.1	Q9Y4X4-1
	KLF12	ENST00000377669.7	TSL:1	c.-32+68077A>G		intron	N/A	ENSP00000366897.2	Q9Y4X4-1
	KLF12	ENST00000885983.1		c.-32+68310A>G		intron	N/A	ENSP00000556042.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83823 AN: 151708 Hom.: 25821 Cov.: 29

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.552 AC: 83822 AN: 151826 Hom.: 25812 Cov.: 29 AF XY: 0.559 AC XY: 41439 AN XY: 74178

African (AFR) AF: 0.267 AC: 11057 AN: 41406

American (AMR) AF: 0.530 AC: 8084 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3468

East Asian (EAS) AF: 0.872 AC: 4483 AN: 5140

South Asian (SAS) AF: 0.799 AC: 3836 AN: 4802

European-Finnish (FIN) AF: 0.690 AC: 7265 AN: 10524

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44893 AN: 67938

Other (OTH) AF: 0.576 AC: 1209 AN: 2100

Alfa AF: 0.572 Hom.: 4510

Bravo AF: 0.526

Asia WGS AF: 0.748 AC: 2604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.61
PhyloP100		-0.43
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: rs9565072; hg19: chr13-74639799;