13-73926833-T-C

Variant names:

• chr13-73926833-T-C
• rs9318227
• NM_001400136.1:c.123+17148A>G

Variant summary

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

The NM_001400136.1(KLF12):​c.123+17148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,788 control chromosomes in the GnomAD database, including 47,607 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 0.78 (47607 hom., cov: 29)
• Consequence: KLF12 NM_001400136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400136.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	NM_001400136.1	MANE Select	c.123+17148A>G		intron	N/A	NP_001387065.1	Q9Y4X4-1
	KLF12	NM_001400139.1		c.123+17148A>G		intron	N/A	NP_001387068.1	Q9Y4X4-1
	KLF12	NM_001400141.1		c.123+17148A>G		intron	N/A	NP_001387070.1	Q9Y4X4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	ENST00000703967.1	MANE Select	c.123+17148A>G		intron	N/A	ENSP00000515592.1	Q9Y4X4-1
	KLF12	ENST00000377669.7	TSL:1	c.123+17148A>G		intron	N/A	ENSP00000366897.2	Q9Y4X4-1
	KLF12	ENST00000885983.1		c.123+17148A>G		intron	N/A	ENSP00000556042.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118744 AN: 151670 Hom.: 47577 Cov.: 29

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.783 AC: 118831 AN: 151788 Hom.: 47607 Cov.: 29 AF XY: 0.787 AC XY: 58409 AN XY: 74182

African (AFR) AF: 0.595 AC: 24582 AN: 41300

American (AMR) AF: 0.807 AC: 12309 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2850 AN: 3468

East Asian (EAS) AF: 0.819 AC: 4210 AN: 5138

South Asian (SAS) AF: 0.855 AC: 4097 AN: 4794

European-Finnish (FIN) AF: 0.883 AC: 9326 AN: 10566

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58841 AN: 67958

Other (OTH) AF: 0.797 AC: 1685 AN: 2114

Alfa AF: 0.838 Hom.: 238138

Bravo AF: 0.768

Asia WGS AF: 0.811 AC: 2821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.9
DANN	Benign	0.74
PhyloP100		-0.25
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: rs9318227; hg19: chr13-74500970;