Genetic Variant NM_001730.5:c.*340T>C (chr13-73076226-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001730.5(KLF5):c.*340T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 203,258 control chromosomes in the GnomAD database, including 189 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 0.026 ( 179 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 10 hom. )

Consequence

KLF5
NM_001730.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.29

Publications

2 publications found

Variant links:

Genes affected

KLF5 (HGNC:6349): (KLF transcription factor 5) This gene encodes a member of the Kruppel-like factor subfamily of zinc finger proteins. The encoded protein is a transcriptional activator that binds directly to a specific recognition motif in the promoters of target genes. This protein acts downstream of multiple different signaling pathways and is regulated by post-translational modification. It may participate in both promoting and suppressing cell proliferation. Expression of this gene may be changed in a variety of different cancers and in cardiovascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

KLF5 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=-0.6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KLF5	NM_001730.5 link	c.*340T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000377687.6	NP_001721.2	Q13887-1Q5T6X2
KLF5	NM_001286818.2 link	c.*340T>C	3_prime_UTR_variant	Exon 4 of 4		NP_001273747.1	Q13887-4
KLF5	XM_047430553.1 link	c.*340T>C	3_prime_UTR_variant	Exon 4 of 4		XP_047286509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF5	ENST00000377687.6 link	c.*340T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001730.5	ENSP00000366915.4		Q13887-1
KLF5	ENST00000539231.5 link	c.*340T>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000440407.1		Q13887-4

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4007

AN:

152046

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0914

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00937

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.00452

AC:

231

AN:

51094

Hom.:

Cov.:

AF XY:

0.00386

AC XY:

AN XY:

25646

show subpopulations

African (AFR)

AF:

0.0870

AC:

176

AN:

2022

American (AMR)

AF:

0.0108

AC:

AN:

1384

Ashkenazi Jewish (ASJ)

AF:

0.00176

AC:

AN:

2274

East Asian (EAS)

AF:

0.00

AC:

AN:

4464

South Asian (SAS)

AF:

0.00

AC:

AN:

488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

332

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

34072

Other (OTH)

AF:

0.00642

AC:

AN:

3582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0263

AC:

4007

AN:

152164

Hom.:

179

Cov.:

AF XY:

0.0253

AC XY:

1881

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0911

AC:

3783

AN:

41508

American (AMR)

AF:

0.00936

AC:

143

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000427

AC:

AN:

67984

Other (OTH)

AF:

0.0194

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

179

358

537

716

895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0151

Hom.:

Bravo

AF:

0.0302

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

3.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over