Variant chr9-107487535-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004235.6(KLF4):c.859C>T(p.His287Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00385 in 1,558,654 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 14 hom. )

Consequence

KLF4
NM_004235.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.59

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:

KLF4 (HGNC:):

KLF4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010651201).

BP6

Variant 9-107487535-G-A is Benign according to our data. Variant chr9-107487535-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3044586.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 469 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF4	NM_004235.6 linkuse as main transcript	c.859C>T	p.His287Tyr	missense_variant	3/5	ENST00000374672.5	NP_004226.3	O43474-1
KLF4	NM_001314052.2 linkuse as main transcript	c.859C>T	p.His287Tyr	missense_variant	3/4		NP_001300981.1	O43474-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLF4	ENST00000374672.5 linkuse as main transcript	c.859C>T	p.His287Tyr	missense_variant	3/5	1	NM_004235.6	ENSP00000363804.4	O43474-1
KLF4	ENST00000493306.1 linkuse as main transcript	n.1124C>T		non_coding_transcript_exon_variant	3/4	1
KLF4	ENST00000610832.1 linkuse as main transcript	c.100-345C>T		intron_variant		5		ENSP00000483629.1	A0A087X0S4
KLF4	ENST00000497048.5 linkuse as main transcript	n.913C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00308

AC:

468

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00522

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00264

AC:

515

AN:

195048

Hom.:

AF XY:

0.00290

AC XY:

307

AN XY:

105698

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.00377

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00393

AC:

5531

AN:

1406508

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

2748

AN XY:

694158

show subpopulations

Gnomad4 AFR exome

AF:

0.000530

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00162

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00277

Gnomad4 FIN exome

AF:

0.00287

Gnomad4 NFE exome

AF:

0.00446

Gnomad4 OTH exome

AF:

0.00352

GnomAD4 genome

AF:

0.00308

AC:

469

AN:

152146

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00522

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.00285

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00263

AC:

317

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KLF4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 04, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.47

M_CAP

Benign

0.014

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Benign

0.12

Sift4G

Benign

0.094

Polyphen

0.99

Vest4

0.63

MVP

0.49

MPC

0.65

ClinPred

0.022

GERP RS

4.9

gMVP

0.27

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over