rs41286082

Variant names:

• chr13-73076226-T-C
• rs41286082
• NM_001730.5:c.*340T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF5	NM_001730.5	c.*340T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000377687.6	NP_001721.2
KLF5	NM_001286818.2	c.*340T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001273747.1
KLF5	XM_047430553.1	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	c.*340T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001730.5	ENSP00000366915.4
KLF5	ENST00000539231.5	c.*340T>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000440407.1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4007 AN: 152046 Hom.: 179 Cov.: 33

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.: 10 Cov.: 0 AF XY: 0.00386 AC XY: 99 AN XY: 25646

Gnomad4 AFR exome AF: 0.0870

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000382

Gnomad4 OTH exome AF: 0.00642

GnomAD4 genome AF: 0.0263 AC: 4007 AN: 152164 Hom.: 179 Cov.: 33 AF XY: 0.0253 AC XY: 1881 AN XY: 74410

Gnomad4 AFR AF: 0.0911

Gnomad4 AMR AF: 0.00936

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000427

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0192 Hom.: 22

Bravo AF: 0.0302

Asia WGS AF: 0.00549 AC: 19 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	15
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs41286082; hg19: chr13-73650364;