2-10049708-C-T

Variant names:

• chr2-10049708-C-T
• rs6432053
• NM_003597.5:c.1258+1113C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

KLF11 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young type 7

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KLF11	NM_003597.5	c.1258+1113C>T		intron_variant	Intron 3 of 3	ENST00000305883.6	NP_003588.1
KLF11	NM_001177716.2	c.1207+1113C>T		intron_variant	Intron 3 of 3		NP_001171187.1
KLF11	NM_001177718.2	c.1207+1113C>T		intron_variant	Intron 3 of 3		NP_001171189.1
KLF11	XM_047446025.1	c.1207+1113C>T		intron_variant	Intron 3 of 3		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6	c.1258+1113C>T		intron_variant	Intron 3 of 3	1	NM_003597.5	ENSP00000307023.1
KLF11	ENST00000535335.1	c.1207+1113C>T		intron_variant	Intron 3 of 3	2		ENSP00000442722.1
KLF11	ENST00000540845.5	c.1207+1113C>T		intron_variant	Intron 3 of 3	2		ENSP00000444690.1

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

African (AFR) AF: 0.442 AC: 18309 AN: 41470

American (AMR) AF: 0.616 AC: 9410 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1754 AN: 3470

East Asian (EAS) AF: 0.679 AC: 3509 AN: 5168

South Asian (SAS) AF: 0.520 AC: 2508 AN: 4826

European-Finnish (FIN) AF: 0.683 AC: 7227 AN: 10586

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34986 AN: 67988

Other (OTH) AF: 0.506 AC: 1069 AN: 2114

Alfa AF: 0.474 Hom.: 4386

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
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6432053; hg19: chr2-10189835;