rs17731

chr10-3779369-G-Achr10-3779369-G-C

Variant summary

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

The NM_001300.6(KLF6):c.*170C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 697,650 control chromosomes in the GnomAD database, including 43,348 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 0.27 (7164 hom., cov: 32)
  • Exomes 𝑓: 0.35 (36184 hom.)
• Consequence: KLF6 NM_001300.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF6	NM_001300.6	c.*170C>T		3_prime_UTR_variant	4/4	ENST00000497571.6
KLF6	NM_001160124.2	c.*170C>T		3_prime_UTR_variant	4/4
KLF6	NM_001160125.2	c.*184C>T		3_prime_UTR_variant	3/3
KLF6	NR_027653.2	n.1063C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF6	ENST00000497571.6	c.*170C>T		3_prime_UTR_variant	4/4	1	NM_001300.6	P1
KLF6	ENST00000542957.1	c.*184C>T		3_prime_UTR_variant	3/3	5
KLF6	ENST00000173785.4	n.603C>T		non_coding_transcript_exon_variant	3/3	2
KLF6	ENST00000461124.1	n.334C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41682 AN: 151972 Hom.: 7169 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.282

GnomAD3 exomes AF: 0.334 AC: 46496 AN: 139352 Hom.: 8397 AF XY: 0.341 AC XY: 25784 AN XY: 75544

Gnomad AFR exome AF: 0.0628

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.476

Gnomad SAS exome AF: 0.344

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.355 AC: 193428 AN: 545560 Hom.: 36184 Cov.: 5 AF XY: 0.358 AC XY: 105563 AN XY: 294840

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.516

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.274 AC: 41666 AN: 152090 Hom.: 7164 Cov.: 32 AF XY: 0.270 AC XY: 20054 AN XY: 74352

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.279

Alfa AF: 0.315 Hom.: 4371

Bravo AF: 0.266

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	13
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17731; hg19: chr10-3821561; COSMIC: COSV51494121; COSMIC: COSV51494121;