rs6650443

Variant names:

• chr13-73713812-G-A
• rs6650443
• ENST00000377669.7:c.1027+1556C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-73713812-G-A
• chr13-73713812-G-C

Variant summary

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

The ENST00000377669.7(KLF12):​c.1027+1556C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,172 control chromosomes in the GnomAD database, including 42,764 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 0.75 (42764 hom., cov: 32)
• Consequence: KLF12 ENST00000377669.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.1027+1556C>T		intron_variant	Intron 7 of 7		NP_001387065.1
KLF12	NM_001400139.1	c.1027+1556C>T		intron_variant	Intron 7 of 7		NP_001387068.1
KLF12	NM_001400141.1	c.1027+1556C>T		intron_variant	Intron 7 of 7		NP_001387070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669.7	c.1027+1556C>T		intron_variant	Intron 7 of 7	1		ENSP00000366897.2
KLF12	ENST00000703967.1	c.1027+1556C>T		intron_variant	Intron 7 of 7			ENSP00000515592.1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113839 AN: 152054 Hom.: 42740 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.749 AC: 113907 AN: 152172 Hom.: 42764 Cov.: 32 AF XY: 0.746 AC XY: 55466 AN XY: 74384

African (AFR) AF: 0.730 AC: 30301 AN: 41512

American (AMR) AF: 0.728 AC: 11134 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2971 AN: 3472

East Asian (EAS) AF: 0.736 AC: 3807 AN: 5172

South Asian (SAS) AF: 0.799 AC: 3857 AN: 4826

European-Finnish (FIN) AF: 0.692 AC: 7315 AN: 10568

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52073 AN: 68012

Other (OTH) AF: 0.760 AC: 1608 AN: 2116

Alfa AF: 0.755 Hom.: 6570

Bravo AF: 0.746

Asia WGS AF: 0.760 AC: 2640 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.45
PhyloP100		-0.057
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: rs6650443; hg19: chr13-74287949;