chr13-73691425-T-C

Variant names:

• chr13-73691425-T-C
• rs7993625
• NM_001400136.1:c.*4065A>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.*4065A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,528 control chromosomes in the GnomAD database, including 31,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.63 (31808 hom., cov: 33)
  • Exomes 𝑓: 0.75 (120 hom.)
• Consequence: KLF12 NM_001400136.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 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.*4065A>G		3_prime_UTR	Exon 8 of 8	NP_001387065.1	Q9Y4X4-1
	KLF12	NM_001400139.1		c.*4065A>G		3_prime_UTR	Exon 8 of 8	NP_001387068.1	Q9Y4X4-1
	KLF12	NM_001400141.1		c.*4065A>G		3_prime_UTR	Exon 8 of 8	NP_001387070.1	Q9Y4X4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	ENST00000703967.1	MANE Select	c.*4065A>G		3_prime_UTR	Exon 8 of 8	ENSP00000515592.1	Q9Y4X4-1
	KLF12	ENST00000377669.7	TSL:1	c.*4065A>G		3_prime_UTR	Exon 8 of 8	ENSP00000366897.2	Q9Y4X4-1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95144 AN: 151982 Hom.: 31813 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.656

GnomAD4 exome AF: 0.750 AC: 321 AN: 428 Hom.: 120 Cov.: 0 AF XY: 0.723 AC XY: 188 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.749 AC: 316 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.626 AC: 95162 AN: 152100 Hom.: 31808 Cov.: 33 AF XY: 0.627 AC XY: 46590 AN XY: 74354

African (AFR) AF: 0.377 AC: 15626 AN: 41476

American (AMR) AF: 0.724 AC: 11059 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2368 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3141 AN: 5166

South Asian (SAS) AF: 0.646 AC: 3110 AN: 4814

European-Finnish (FIN) AF: 0.725 AC: 7674 AN: 10588

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50054 AN: 67990

Other (OTH) AF: 0.651 AC: 1374 AN: 2110

Alfa AF: 0.697 Hom.: 54822

Bravo AF: 0.618

Asia WGS AF: 0.606 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		-0.089
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: rs7993625; hg19: chr13-74265562;