chr2-10043613-C-T

Position:

• chr2-10043613-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000305883.6(KLF11):​c.-104C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 801,140 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (3 hom.)
• Consequence: KLF11 ENST00000305883.6 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.309

Genes affected

KLF11 (HGNC:11811): (KLF transcription factor 11) The protein encoded by this gene is a zinc finger transcription factor that binds to SP1-like sequences in epsilon- and gamma-globin gene promoters. This binding inhibits cell growth and causes apoptosis. Defects in this gene are a cause of maturity-onset diabetes of the young type 7 (MODY7). Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS2: High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF11	NM_003597.5	c.-104C>T		5_prime_UTR_variant	1/4	ENST00000305883.6	NP_003588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6	c.-104C>T		5_prime_UTR_variant	1/4	1	NM_003597.5	ENSP00000307023	A2
KLF11	ENST00000401510.5	c.-10+542C>T		intron_variant		3		ENSP00000386058

Frequencies

GnomAD3 genomes AF: 0.000406 AC: 55 AN: 135620 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00107

Gnomad ASJ AF: 0.00594

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000225

Gnomad OTH AF: 0.00109

GnomAD4 exome AF: 0.000206 AC: 137 AN: 665438 Hom.: 3 Cov.: 9 AF XY: 0.000189 AC XY: 60 AN XY: 316778

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000789

Gnomad4 ASJ exome AF: 0.00682

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000252

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.000500

GnomAD4 genome AF: 0.000405 AC: 55 AN: 135702 Hom.: 0 Cov.: 31 AF XY: 0.000363 AC XY: 24 AN XY: 66102

Gnomad4 AFR AF: 0.000138

Gnomad4 AMR AF: 0.00107

Gnomad4 ASJ AF: 0.00594

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000225

Gnomad4 OTH AF: 0.00108

Alfa AF: 0.000327 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Maturity-onset diabetes of the young type 7 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.86

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: rs886054718; hg19: chr2-10183740;