Variant rs186624120 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM1BP4_StrongBS1_SupportingBS2

The ENST00000469435.1(KLF6):c.737C>T(p.Ala246Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000892 in 1,599,390 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 14 hom. )

Consequence

KLF6
ENST00000469435.1 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

KLF6 (HGNC:2235): (KLF transcription factor 6) This gene encodes a member of the Kruppel-like family of transcription factors. The zinc finger protein is a transcriptional activator, and functions as a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene, some of which are implicated in carcinogenesis. [provided by RefSeq, May 2009]

KLF6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM1

In a chain Krueppel-like factor 6 (size 282) in uniprot entity KLF6_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in ENST00000469435.1

BP4

Computational evidence support a benign effect (MetaRNN=0.004200399).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00491 (748/152356) while in subpopulation AFR AF= 0.0171 (711/41594). AF 95% confidence interval is 0.0161. There are 4 homozygotes in gnomad4. There are 366 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 748 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KLF6	NM_001300.6 linkuse as main transcript	c.676+61C>T	intron_variant	ENST00000497571.6	NP_001291.3
KLF6	NM_001160124.2 linkuse as main transcript	c.550+187C>T	intron_variant		NP_001153596.1
KLF6	NM_001160125.2 linkuse as main transcript	c.676+61C>T	intron_variant		NP_001153597.1
KLF6	NR_027653.2 linkuse as main transcript	n.717+215C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF6	ENST00000469435.1 linkuse as main transcript	c.737C>T	p.Ala246Val	missense_variant	2/2	1		ENSP00000419079		Q99612-2
KLF6	ENST00000497571.6 linkuse as main transcript	c.676+61C>T		intron_variant		1	NM_001300.6	ENSP00000419923	P1	Q99612-1
KLF6	ENST00000542957.1 linkuse as main transcript	c.676+61C>T		intron_variant		5		ENSP00000445301		Q99612-3
KLF6	ENST00000173785.4 linkuse as main transcript	n.257+215C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00491

AC:

747

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00106

AC:

230

AN:

216630

Hom.:

AF XY:

0.000827

AC XY:

AN XY:

118450

show subpopulations

Gnomad AFR exome

AF:

0.0168

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000321

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000469

AC:

679

AN:

1447034

Hom.:

Cov.:

AF XY:

0.000383

AC XY:

275

AN XY:

718872

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.000644

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000145

Gnomad4 OTH exome

AF:

0.00122

GnomAD4 genome

AF:

0.00491

AC:

748

AN:

152356

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

366

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00526

ExAC

AF:

0.00143

AC:

171

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;N

PROVEAN

Benign

-0.52

REVEL

Benign

0.042

Sift

Uncertain

0.011

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.12

MVP

0.44

ClinPred

0.015

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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