Genetic Variant KLF6:c.*2522G>A (chr10-3777017-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.*2522G>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 0.102 in 513,968 control chromosomes in the GnomAD database, including 3,290 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 0.096 ( 888 hom., cov: 30)

Exomes 𝑓: 0.11 ( 2402 hom. )

Consequence

KLF6
NM_001300.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.582

Publications

8 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=-0.47).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLF6	NM_001300.6	MANE Select	c.*2522G>A	3_prime_UTR	Exon 4 of 4	NP_001291.3
KLF6	NM_001160124.2		c.*2522G>A	3_prime_UTR	Exon 4 of 4	NP_001153596.1	D3GC14
KLF6	NM_001160125.2		c.*2536G>A	3_prime_UTR	Exon 3 of 3	NP_001153597.1	Q99612-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLF6	ENST00000497571.6	TSL:1 MANE Select	c.*2522G>A	3_prime_UTR	Exon 4 of 4	ENSP00000419923.1	Q99612-1
KLF6	ENST00000542957.1	TSL:5	c.*2536G>A	3_prime_UTR	Exon 3 of 3	ENSP00000445301.1	Q99612-3
KLF6	ENST00000461124.1	TSL:5	n.357-614G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0957

AC:

14375

AN:

150136

Hom.:

888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0604

Gnomad EAS

AF:

0.0506

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.0883

GnomAD2 exomes

AF:

0.101

AC:

13232

AN:

130470

AF XY:

0.0958

show subpopulations

Gnomad AFR exome

AF:

0.0194

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.0665

Gnomad EAS exome

AF:

0.0501

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.0959

GnomAD4 exome

AF:

0.105

AC:

38264

AN:

363724

Hom.:

2402

Cov.:

AF XY:

0.0996

AC XY:

19975

AN XY:

200572

show subpopulations

African (AFR)

AF:

0.0231

AC:

264

AN:

11404

American (AMR)

AF:

0.132

AC:

3852

AN:

29080

Ashkenazi Jewish (ASJ)

AF:

0.0664

AC:

978

AN:

14736

East Asian (EAS)

AF:

0.0592

AC:

1095

AN:

18506

South Asian (SAS)

AF:

0.0412

AC:

2482

AN:

60174

European-Finnish (FIN)

AF:

0.180

AC:

2233

AN:

12404

Middle Eastern (MID)

AF:

0.0289

AC:

AN:

1520

European-Non Finnish (NFE)

AF:

0.129

AC:

25433

AN:

196590

Other (OTH)

AF:

0.0975

AC:

1883

AN:

19310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2129

4258

6386

8515

10644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0957

AC:

14377

AN:

150244

Hom.:

888

Cov.:

AF XY:

0.0978

AC XY:

7164

AN XY:

73260

show subpopulations

African (AFR)

AF:

0.0257

AC:

1048

AN:

40792

American (AMR)

AF:

0.106

AC:

1589

AN:

15022

Ashkenazi Jewish (ASJ)

AF:

0.0604

AC:

209

AN:

3462

East Asian (EAS)

AF:

0.0509

AC:

262

AN:

5146

South Asian (SAS)

AF:

0.0448

AC:

214

AN:

4782

European-Finnish (FIN)

AF:

0.202

AC:

2039

AN:

10114

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.129

AC:

8757

AN:

67640

Other (OTH)

AF:

0.0873

AC:

182

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

625

1249

1874

2498

3123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

585

Bravo

AF:

0.0880

Asia WGS

AF:

0.0490

AC:

173

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.58

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over