rs2236599

chr9-107487224-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004235.6(KLF4):c.1100-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,609,242 control chromosomes in the GnomAD database, including 27,499 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 0.15 (2217 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25282 hom.)
• Consequence: KLF4 NM_004235.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

Genes affected

KLF4 (HGNC:6348): (KLF transcription factor 4) This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is required for normal development of the barrier function of skin. The encoded protein is thought to control the G1-to-S transition of the cell cycle following DNA damage by mediating the tumor suppressor gene p53. Mice lacking this gene have a normal appearance but lose weight rapidly, and die shortly after birth due to fluid evaporation resulting from compromised epidermal barrier function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF4	NM_004235.6	c.1100-32G>A		intron_variant		ENST00000374672.5
KLF4	NM_001314052.2	c.1170G>A	p.Gly390=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF4	ENST00000374672.5	c.1100-32G>A		intron_variant		1	NM_004235.6	P1
KLF4	ENST00000493306.1	n.1435G>A		non_coding_transcript_exon_variant	3/4	1
KLF4	ENST00000610832.1	c.100-34G>A		intron_variant		5
KLF4	ENST00000497048.5	n.1154-32G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22965 AN: 151968 Hom.: 2218 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.171

GnomAD3 exomes AF: 0.184 AC: 45312 AN: 246782 Hom.: 4748 AF XY: 0.182 AC XY: 24289 AN XY: 133114

Gnomad AFR exome AF: 0.0327

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.288

Gnomad SAS exome AF: 0.0855

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.190

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.181 AC: 263912 AN: 1457156 Hom.: 25282 Cov.: 34 AF XY: 0.179 AC XY: 129511 AN XY: 724372

Gnomad4 AFR exome AF: 0.0277

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.0839

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.151 AC: 22951 AN: 152086 Hom.: 2217 Cov.: 32 AF XY: 0.153 AC XY: 11385 AN XY: 74296

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.170

Alfa AF: 0.166 Hom.: 1404

Bravo AF: 0.144

Asia WGS AF: 0.201 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2236599; hg19: chr9-110249505; COSMIC: COSV65928618; COSMIC: COSV65928618;