chr13-74123719-T-G

Variant names:

• chr13-74123719-T-G
• rs4885151
• NM_001400136.1:c.-32+10253A>C

Variant summary

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

The NM_001400136.1(KLF12):​c.-32+10253A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,136 control chromosomes in the GnomAD database, including 27,568 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 0.54 (27568 hom., cov: 33)
• Consequence: KLF12 NM_001400136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715
• Publications: 9 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 (EAS) allele frequency at 95% confidence interval = 0.865 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.-32+10253A>C		intron	N/A	NP_001387065.1	Q9Y4X4-1
	KLF12	NM_001400139.1		c.-31-128666A>C		intron	N/A	NP_001387068.1	Q9Y4X4-1
	KLF12	NM_007249.5		c.-32+10020A>C		intron	N/A	NP_009180.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	ENST00000703967.1	MANE Select	c.-32+10253A>C		intron	N/A	ENSP00000515592.1	Q9Y4X4-1
	KLF12	ENST00000377669.7	TSL:1	c.-32+10020A>C		intron	N/A	ENSP00000366897.2	Q9Y4X4-1
	KLF12	ENST00000885983.1		c.-32+10253A>C		intron	N/A	ENSP00000556042.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82722 AN: 152018 Hom.: 27570 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.544 AC: 82724 AN: 152136 Hom.: 27568 Cov.: 33 AF XY: 0.546 AC XY: 40595 AN XY: 74360

African (AFR) AF: 0.141 AC: 5837 AN: 41508

American (AMR) AF: 0.649 AC: 9911 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2149 AN: 3468

East Asian (EAS) AF: 0.886 AC: 4590 AN: 5180

South Asian (SAS) AF: 0.550 AC: 2655 AN: 4826

European-Finnish (FIN) AF: 0.729 AC: 7707 AN: 10574

Middle Eastern (MID) AF: 0.552 AC: 159 AN: 288

European-Non Finnish (NFE) AF: 0.708 AC: 48168 AN: 67988

Other (OTH) AF: 0.557 AC: 1177 AN: 2114

Alfa AF: 0.657 Hom.: 57745

Bravo AF: 0.528

Asia WGS AF: 0.626 AC: 2175 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.47
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4885151; hg19: chr13-74697856;