8-102649114-G-T

Position:

• chr8-102649114-G-T

Variant summary

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

The ENST00000285407.11(KLF10):​c.*1018C>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 0.452 in 149,092 control chromosomes in the GnomAD database, including 15,302 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 0.45 (15260 hom., cov: 32)
  • Exomes 𝑓: 0.42 (42 hom.)
• Consequence: KLF10 ENST00000285407.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

Genes affected

KLF10 (HGNC:11810): (KLF transcription factor 10) This gene encodes a member of a family of proteins that feature C2H2-type zinc finger domains. The encoded protein is a transcriptional repressor that acts as an effector of transforming growth factor beta signaling. Activity of this protein may inhibit the growth of cancers, particularly pancreatic cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF10	NM_005655.4	c.*1018C>A		3_prime_UTR_variant	4/4	ENST00000285407.11	NP_005646.1
KLF10	NM_001032282.4	c.*1018C>A		3_prime_UTR_variant	4/4		NP_001027453.1
KLF10	NR_103759.2	n.1786C>A		non_coding_transcript_exon_variant	3/3
KLF10	NR_103760.2	n.1909C>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF10	ENST00000285407.11	c.*1018C>A		3_prime_UTR_variant	4/4	1	NM_005655.4	ENSP00000285407	P1
KLF10	ENST00000395884.3	c.*1018C>A		3_prime_UTR_variant	4/4	1		ENSP00000379222

Frequencies

GnomAD3 genomes AF: 0.452 AC: 67194 AN: 148560 Hom.: 15249 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.419 AC: 180 AN: 430 Hom.: 42 Cov.: 0 AF XY: 0.438 AC XY: 113 AN XY: 258

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.452 AC: 67235 AN: 148662 Hom.: 15260 Cov.: 32 AF XY: 0.453 AC XY: 32910 AN XY: 72670

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.451

Alfa AF: 0.359 Hom.: 1310

Bravo AF: 0.448

Asia WGS AF: 0.503 AC: 1745 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6935; hg19: chr8-103661342;