2-10049708-C-T

Position:

• chr2-10049708-C-T

Variant summary

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

The NM_003597.5(KLF11):​c.1258+1113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,104 control chromosomes in the GnomAD database, including 21,014 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 0.52 (21014 hom., cov: 32)
• Consequence: KLF11 NM_003597.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF11	NM_003597.5	c.1258+1113C>T		intron_variant		ENST00000305883.6
KLF11	NM_001177716.2	c.1207+1113C>T		intron_variant
KLF11	NM_001177718.2	c.1207+1113C>T		intron_variant
KLF11	XM_047446025.1	c.1207+1113C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF11	ENST00000305883.6	c.1258+1113C>T		intron_variant		1	NM_003597.5	A2
KLF11	ENST00000535335.1	c.1207+1113C>T		intron_variant		2		P4
KLF11	ENST00000540845.5	c.1207+1113C>T		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79183 AN: 151984 Hom.: 21006 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.521 AC: 79217 AN: 152104 Hom.: 21014 Cov.: 32 AF XY: 0.531 AC XY: 39461 AN XY: 74352

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.506

Alfa AF: 0.475 Hom.: 4313

Bravo AF: 0.513

Asia WGS AF: 0.562 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.19

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: rs6432053; hg19: chr2-10189835;