Genetic Variant NM_001300.6:c.*62G>A (chr10-3779477-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001300.6(KLF6):c.*62G>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 0.00299 in 1,419,224 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.014 ( 63 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 52 hom. )

Consequence

KLF6
NM_001300.6 3_prime_UTR

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 2.74

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0144 (2195/152318) while in subpopulation AFR AF = 0.0496 (2059/41552). AF 95% confidence interval is 0.0478. There are 63 homozygotes in GnomAd4. There are 1002 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 2195 AD gene.

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.*62G>A	3_prime_UTR	Exon 4 of 4	NP_001291.3
KLF6	NM_001160124.2		c.*62G>A	3_prime_UTR	Exon 4 of 4	NP_001153596.1	D3GC14
KLF6	NM_001160125.2		c.*76G>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.*62G>A	3_prime_UTR	Exon 4 of 4	ENSP00000419923.1	Q99612-1
KLF6	ENST00000875520.1		c.*62G>A	3_prime_UTR	Exon 4 of 4	ENSP00000545579.1
KLF6	ENST00000875519.1		c.*62G>A	3_prime_UTR	Exon 4 of 4	ENSP00000545578.1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2182

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00391

AC:

972

AN:

248806

AF XY:

0.00293

show subpopulations

Gnomad AFR exome

AF:

0.0507

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000214

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00162

AC:

2054

AN:

1266906

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

894

AN XY:

639846

show subpopulations

African (AFR)

AF:

0.0510

AC:

1522

AN:

29818

American (AMR)

AF:

0.00384

AC:

170

AN:

44284

Ashkenazi Jewish (ASJ)

AF:

0.0000402

AC:

AN:

24882

East Asian (EAS)

AF:

0.00

AC:

AN:

38830

South Asian (SAS)

AF:

0.000170

AC:

AN:

82128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53242

Middle Eastern (MID)

AF:

0.00412

AC:

AN:

5336

European-Non Finnish (NFE)

AF:

0.000111

AC:

104

AN:

934576

Other (OTH)

AF:

0.00411

AC:

221

AN:

53810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

118

236

353

471

589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.0144

AC:

2195

AN:

152318

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1002

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0496

AC:

2059

AN:

41552

American (AMR)

AF:

0.00614

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68030

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

101

202

302

403

504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00839

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypotension (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

2.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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