rs1887346

Positions:

• chr13-73918865-G-A
• chr13-73918865-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377669.7(KLF12):​c.123+25116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,964 control chromosomes in the GnomAD database, including 4,781 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 0.24 (4781 hom., cov: 32)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF12	NM_001400136.1	c.123+25116C>T		intron_variant		ENST00000703967.1
KLF12	NM_001400153.1	c.123+25116C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF12	ENST00000703967.1	c.123+25116C>T		intron_variant			NM_001400136.1	P1
KLF12	ENST00000377669.7	c.123+25116C>T		intron_variant		1		P1
KLF12	ENST00000472022.1	n.157+25116C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35977 AN: 151846 Hom.: 4777 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.237 AC: 36002 AN: 151964 Hom.: 4781 Cov.: 32 AF XY: 0.241 AC XY: 17932 AN XY: 74284

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.218

Alfa AF: 0.251 Hom.: 6694

Bravo AF: 0.223

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1887346; hg19: chr13-74493002;