rs1927010

Positions:

• chr13-73848392-T-A
• chr13-73848392-T-G

Variant summary

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

The ENST00000377669.7(KLF12):​c.124-2019A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,714 control chromosomes in the GnomAD database, including 26,745 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 0.58 (26745 hom., cov: 30)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.124-2019A>T		intron_variant		ENST00000703967.1	NP_001387065.1
KLF12	NM_001400153.1	c.124-2019A>T		intron_variant			NP_001387082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000703967.1	c.124-2019A>T		intron_variant			NM_001400136.1	ENSP00000515592	P1
KLF12	ENST00000377669.7	c.124-2019A>T		intron_variant		1		ENSP00000366897	P1
KLF12	ENST00000472022.1	n.158-2019A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88277 AN: 151602 Hom.: 26732 Cov.: 30

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.582 AC: 88334 AN: 151714 Hom.: 26745 Cov.: 30 AF XY: 0.586 AC XY: 43440 AN XY: 74128

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.559

Alfa AF: 0.620 Hom.: 3722

Bravo AF: 0.557

Asia WGS AF: 0.641 AC: 2227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.81

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: rs1927010; hg19: chr13-74422529;