rs1886512

Variant names:

• chr13-73946049-T-A
• rs1886512
• NM_001400136.1:c.34-1979A>T

Variant summary

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

The NM_001400136.1(KLF12):​c.34-1979A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,900 control chromosomes in the GnomAD database, including 12,068 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 (12068 hom., cov: 31)
• Consequence: KLF12 NM_001400136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 34 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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.34-1979A>T		intron_variant	Intron 2 of 7	ENST00000703967.1	NP_001387065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000703967.1	c.34-1979A>T		intron_variant	Intron 2 of 7		NM_001400136.1	ENSP00000515592.1
KLF12	ENST00000377669.7	c.34-1979A>T		intron_variant	Intron 2 of 7	1		ENSP00000366897.2
KLF12	ENST00000472022.1	n.68-1979A>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59679 AN: 151782 Hom.: 12069 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.393 AC: 59717 AN: 151900 Hom.: 12068 Cov.: 31 AF XY: 0.391 AC XY: 28986 AN XY: 74224

African (AFR) AF: 0.471 AC: 19499 AN: 41412

American (AMR) AF: 0.347 AC: 5291 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1331 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1320 AN: 5158

South Asian (SAS) AF: 0.380 AC: 1827 AN: 4812

European-Finnish (FIN) AF: 0.355 AC: 3742 AN: 10538

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25437 AN: 67938

Other (OTH) AF: 0.405 AC: 856 AN: 2114

Alfa AF: 0.373 Hom.: 6077

Bravo AF: 0.395

Asia WGS AF: 0.341 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.5
DANN	Benign	0.81
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1886512; hg19: chr13-74520186; COSMIC: COSV66580605;