Genetic Variant KLF6:c.*2017G>A (chr10-3777522-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001300.6(KLF6):c.*2017G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 511,580 control chromosomes in the GnomAD database, including 30,959 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 0.27 ( 7268 hom., cov: 31)

Exomes 𝑓: 0.35 ( 23691 hom. )

Consequence

KLF6
NM_001300.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.846

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KLF6	NM_001300.6 link	c.*2017G>A	3_prime_UTR_variant	Exon 4 of 4	ENST00000497571.6	NP_001291.3	Q99612-1
KLF6	NR_027653.2 link	n.2910G>A	non_coding_transcript_exon_variant	Exon 4 of 4
KLF6	NM_001160124.2 link	c.*2017G>A	3_prime_UTR_variant	Exon 4 of 4		NP_001153596.1	Q99612D3GC14
KLF6	NM_001160125.2 link	c.*2031G>A	3_prime_UTR_variant	Exon 3 of 3		NP_001153597.1	Q99612-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KLF6	ENST00000497571.6 link	c.*2017G>A	3_prime_UTR_variant	Exon 4 of 4	1	NM_001300.6	ENSP00000419923.1	Q99612-1
KLF6	ENST00000542957.1 link	c.*2031G>A	3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000445301.1	Q99612-3
KLF6	ENST00000461124.1 link	n.357-1119G>A	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41799

AN:

151852

Hom.:

7273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0680

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.282

GnomAD2 exomes

AF:

0.335

AC:

43768

AN:

130470

AF XY:

0.343

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.353

AC:

126907

AN:

359608

Hom.:

23691

Cov.:

AF XY:

0.358

AC XY:

71133

AN XY:

198722

show subpopulations

African (AFR)

AF:

0.0599

AC:

668

AN:

11146

American (AMR)

AF:

0.262

AC:

7584

AN:

28908

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

4839

AN:

14516

East Asian (EAS)

AF:

0.507

AC:

9144

AN:

18036

South Asian (SAS)

AF:

0.353

AC:

21220

AN:

60168

European-Finnish (FIN)

AF:

0.267

AC:

3316

AN:

12404

Middle Eastern (MID)

AF:

0.378

AC:

570

AN:

1506

European-Non Finnish (NFE)

AF:

0.378

AC:

73356

AN:

194110

Other (OTH)

AF:

0.330

AC:

6210

AN:

18814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4807

9613

14420

19226

24033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.275

AC:

41784

AN:

151972

Hom.:

7268

Cov.:

AF XY:

0.270

AC XY:

20081

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0678

AC:

2810

AN:

41476

American (AMR)

AF:

0.266

AC:

4063

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1180

AN:

3472

East Asian (EAS)

AF:

0.501

AC:

2587

AN:

5164

South Asian (SAS)

AF:

0.335

AC:

1613

AN:

4814

European-Finnish (FIN)

AF:

0.258

AC:

2712

AN:

10520

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.379

AC:

25723

AN:

67946

Other (OTH)

AF:

0.279

AC:

591

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1387

2773

4160

5546

6933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.334

Hom.:

4094

Bravo

AF:

0.267

Asia WGS

AF:

0.336

AC:

1165

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.3

(source)

DANN

Benign

0.72

PhyloP100

0.85

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr10-3777522-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over