rs9600167

Variant names:

• chr13-73763608-C-G
• rs9600167
• ENST00000377669.7:c.869+1330G>C

Variant summary

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

The ENST00000377669.7(KLF12):​c.869+1330G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,940 control chromosomes in the GnomAD database, including 10,407 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 0.35 (10407 hom., cov: 32)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.41
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.869+1330G>C		intron_variant	Intron 6 of 7		NP_001387065.1
KLF12	NM_001400139.1	c.869+1330G>C		intron_variant	Intron 6 of 7		NP_001387068.1
KLF12	NM_001400141.1	c.869+1330G>C		intron_variant	Intron 6 of 7		NP_001387070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7	c.869+1330G>C		intron_variant	Intron 6 of 7	1		ENSP00000366897.2
KLF12	ENST00000703967.1	c.869+1330G>C		intron_variant	Intron 6 of 7			ENSP00000515592.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53432 AN: 151822 Hom.: 10386 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.352 AC: 53497 AN: 151940 Hom.: 10407 Cov.: 32 AF XY: 0.343 AC XY: 25473 AN XY: 74260

African (AFR) AF: 0.519 AC: 21470 AN: 41386

American (AMR) AF: 0.291 AC: 4444 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3468

East Asian (EAS) AF: 0.117 AC: 608 AN: 5176

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4812

European-Finnish (FIN) AF: 0.181 AC: 1916 AN: 10560

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21251 AN: 67970

Other (OTH) AF: 0.369 AC: 779 AN: 2110

Alfa AF: 0.333 Hom.: 1122

Bravo AF: 0.369

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0040
DANN	Benign	0.65
PhyloP100		-4.4
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: rs9600167; hg19: chr13-74337745;