rs4885065

chr13-73075497-G-Achr13-73075497-G-Cchr13-73075497-G-T

Variant summary

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

The NM_001730.5(KLF5):c.1196-211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,126 control chromosomes in the GnomAD database, including 50,029 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 0.81 (50029 hom., cov: 31)
• Consequence: KLF5 NM_001730.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF5	NM_001730.5	c.1196-211G>A		intron_variant		ENST00000377687.6
KLF5	NM_001286818.2	c.923-211G>A		intron_variant
KLF5	XM_047430553.1	c.974-211G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF5	ENST00000377687.6	c.1196-211G>A		intron_variant		1	NM_001730.5	P3
KLF5	ENST00000539231.5	c.923-211G>A		intron_variant		1		A1
KLF5	ENST00000464404.2	n.60-211G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123047 AN: 152008 Hom.: 50001 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.811

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.809 AC: 123127 AN: 152126 Hom.: 50029 Cov.: 31 AF XY: 0.811 AC XY: 60356 AN XY: 74394

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.813

Alfa AF: 0.830 Hom.: 74265

Bravo AF: 0.806

Asia WGS AF: 0.845 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.0060
Dann	Benign	0.55

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: rs4885065; hg19: chr13-73649635;