rs8000245

Variant names:

• chr13-74156255-C-T
• rs8000245
• NM_001400139.1:c.-32+149741G>A

Variant summary

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

The NM_001400139.1(KLF12):​c.-32+149741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,120 control chromosomes in the GnomAD database, including 2,917 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 0.18 (2917 hom., cov: 32)
• Consequence: KLF12 NM_001400139.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF12	NM_001400139.1	c.-32+149741G>A		intron_variant	Intron 1 of 7		NP_001387068.1
KLF12	NM_001400153.1	c.-32+149741G>A		intron_variant	Intron 1 of 6		NP_001387082.1
KLF12	XM_011534909.3	c.-32+11894G>A		intron_variant	Intron 1 of 7		XP_011533211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27373 AN: 152002 Hom.: 2909 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.180 AC: 27409 AN: 152120 Hom.: 2917 Cov.: 32 AF XY: 0.181 AC XY: 13429 AN XY: 74388

African (AFR) AF: 0.295 AC: 12217 AN: 41448

American (AMR) AF: 0.135 AC: 2058 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3472

East Asian (EAS) AF: 0.0955 AC: 495 AN: 5184

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4820

European-Finnish (FIN) AF: 0.154 AC: 1626 AN: 10586

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8804 AN: 68002

Other (OTH) AF: 0.176 AC: 371 AN: 2112

Alfa AF: 0.150 Hom.: 4529

Bravo AF: 0.180

Asia WGS AF: 0.184 AC: 641 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	8.3
DANN	Benign	0.81
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs8000245; hg19: chr13-74730392;