9-107487224-C-T

Variant names:

• chr9-107487224-C-T
• rs2236599
• NM_004235.6:c.1100-32G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001314052.2(KLF4):​c.1170G>A​(p.Gly390Gly) variant causes a synonymous 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_001314052.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 22 publications found

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]

KLF4 Gene-Disease associations (from GenCC):

• epidermal disease

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.079 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001314052.2. 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
	KLF4	NM_004235.6	MANE Select	c.1100-32G>A		intron	N/A	NP_004226.3
	KLF4	NM_001314052.2		c.1170G>A	p.Gly390Gly	synonymous	Exon 3 of 4	NP_001300981.1	O43474-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF4	ENST00000374672.5	TSL:1 MANE Select	c.1100-32G>A		intron	N/A	ENSP00000363804.4	O43474-1
	KLF4	ENST00000493306.1	TSL:1	n.1435G>A		non_coding_transcript_exon	Exon 3 of 4
	KLF4	ENST00000610832.1	TSL:5	c.100-34G>A		intron	N/A	ENSP00000483629.1	A0A087X0S4

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

GnomAD2 exomes AF: 0.184 AC: 45312 AN: 246782 AF XY: 0.182

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 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

African (AFR) AF: 0.0277 AC: 926 AN: 33426

American (AMR) AF: 0.187 AC: 8295 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6188 AN: 25662

East Asian (EAS) AF: 0.274 AC: 10890 AN: 39674

South Asian (SAS) AF: 0.0839 AC: 7173 AN: 85474

European-Finnish (FIN) AF: 0.267 AC: 14181 AN: 53212

Middle Eastern (MID) AF: 0.154 AC: 882 AN: 5742

European-Non Finnish (NFE) AF: 0.184 AC: 204157 AN: 1109312

Other (OTH) AF: 0.186 AC: 11220 AN: 60206

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

African (AFR) AF: 0.0362 AC: 1505 AN: 41540

American (AMR) AF: 0.166 AC: 2544 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3466

East Asian (EAS) AF: 0.281 AC: 1441 AN: 5130

South Asian (SAS) AF: 0.0870 AC: 419 AN: 4814

European-Finnish (FIN) AF: 0.272 AC: 2866 AN: 10556

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12721 AN: 67972

Other (OTH) AF: 0.170 AC: 360 AN: 2114

Alfa AF: 0.167 Hom.: 1818

Bravo AF: 0.144

Asia WGS AF: 0.201 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.079
BranchPoint Hunter		0.0
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: rs2236599; hg19: chr9-110249505; COSMIC: COSV65928618; COSMIC: COSV65928618;