Variant NM_004235.6:c.1100-32G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.15 ( 2217 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25282 hom. )

Consequence

KLF4
NM_004235.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0790

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 rank	MANE	Protein	UniProt
KLF4	NM_004235.6 link	c.1100-32G>A		intron_variant	Intron 3 of 4	ENST00000374672.5	NP_004226.3	O43474-1
KLF4	NM_001314052.2 link	c.1170G>A	p.Gly390Gly	synonymous_variant	Exon 3 of 4		NP_001300981.1	O43474-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KLF4	ENST00000374672.5 link	c.1100-32G>A	intron_variant	Intron 3 of 4	1	NM_004235.6	ENSP00000363804.4	O43474-1
KLF4	ENST00000493306.1 link	n.1435G>A	non_coding_transcript_exon_variant	Exon 3 of 4	1
KLF4	ENST00000610832.1 link	c.100-34G>A	intron_variant	Intron 2 of 3	5		ENSP00000483629.1	A0A087X0S4
KLF4	ENST00000497048.5 link	n.1154-32G>A	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22965

AN:

151968

Hom.:

2218

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.179

AC XY:

129511

AN XY:

724372

show subpopulations

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.:

AF XY:

0.153

AC XY:

11385

AN XY:

74296

show subpopulations

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

BranchPoint Hunter

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over