rs3764109

Variant names:

• chr13-73862019-T-C
• rs3764109
• ENST00000377669.7:c.124-15646A>G

Variant summary

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

The ENST00000377669.7(KLF12):​c.124-15646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,110 control chromosomes in the GnomAD database, including 18,431 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 0.49 (18431 hom., cov: 30)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.124-15646A>G		intron_variant	Intron 3 of 7		NP_001387065.1
KLF12	NM_001400139.1	c.124-15646A>G		intron_variant	Intron 3 of 7		NP_001387068.1
KLF12	NM_001400141.1	c.124-15646A>G		intron_variant	Intron 3 of 7		NP_001387070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7	c.124-15646A>G		intron_variant	Intron 3 of 7	1		ENSP00000366897.2
KLF12	ENST00000703967.1	c.124-15646A>G		intron_variant	Intron 3 of 7			ENSP00000515592.1
KLF12	ENST00000472022.1	n.158-15646A>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73338 AN: 151002 Hom.: 18437 Cov.: 30

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.485 AC: 73336 AN: 151110 Hom.: 18431 Cov.: 30 AF XY: 0.479 AC XY: 35331 AN XY: 73752

African (AFR) AF: 0.450 AC: 18549 AN: 41196

American (AMR) AF: 0.421 AC: 6371 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2044 AN: 3470

East Asian (EAS) AF: 0.161 AC: 819 AN: 5100

South Asian (SAS) AF: 0.432 AC: 2065 AN: 4784

European-Finnish (FIN) AF: 0.472 AC: 4859 AN: 10298

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36728 AN: 67840

Other (OTH) AF: 0.496 AC: 1041 AN: 2098

Alfa AF: 0.520 Hom.: 65329

Bravo AF: 0.479

Asia WGS AF: 0.302 AC: 1058 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.70
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3764109; hg19: chr13-74436156; COSMIC: COSV66580481;