Genetic Variant KLF6:p.Arg201Arg (chr10-3781714-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001300.6(KLF6):c.603G>A(p.Arg201Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,614,124 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 97 hom. )

Consequence

KLF6
NM_001300.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.591

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 10-3781714-C-T is Benign according to our data. Variant chr10-3781714-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 132786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.591 with no splicing effect.

BS2

High AC in GnomAd4 at 1125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF6	NM_001300.6 link	c.603G>A	p.Arg201Arg	synonymous_variant	Exon 2 of 4	ENST00000497571.6	NP_001291.3	Q99612-1
KLF6	NM_001160125.2 link	c.603G>A	p.Arg201Arg	synonymous_variant	Exon 2 of 3		NP_001153597.1	Q99612-3
KLF6	NM_001160124.2 link	c.550+53G>A		intron_variant	Intron 2 of 3		NP_001153596.1	Q99612D3GC14
KLF6	NR_027653.2 link	n.717+81G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF6	ENST00000497571.6 link	c.603G>A	p.Arg201Arg	synonymous_variant	Exon 2 of 4	1	NM_001300.6	ENSP00000419923.1		Q99612-1

Frequencies

GnomAD3 genomes

AF:

0.00739

AC:

1125

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0336

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00910

Gnomad OTH

AF:

0.00288

GnomAD2 exomes

AF:

0.00769

AC:

1930

AN:

250900

AF XY:

0.00783

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.00906

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00946

AC:

13824

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00942

AC XY:

6852

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

33480

American (AMR)

AF:

0.00204

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.000804

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00159

AC:

137

AN:

86250

European-Finnish (FIN)

AF:

0.0306

AC:

1632

AN:

53412

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0103

AC:

11414

AN:

1111968

Other (OTH)

AF:

0.00752

AC:

454

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

903

1806

2710

3613

4516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00739

AC:

1125

AN:

152308

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

619

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41574

American (AMR)

AF:

0.00333

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00290

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0336

AC:

357

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00910

AC:

619

AN:

68024

Other (OTH)

AF:

0.00285

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00749

Hom.:

Bravo

AF:

0.00533

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.00871

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KLF6: BP4, BP7, BS2 -

Hypotension

Other:1

Centre for molecular medicine, Karolinska Institutet

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.0

(source)

DANN

Benign

0.95

PhyloP100

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=93/7

polymorphism

(source)

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

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chr10-3781714-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over