Genetic Variant KLF11:c.-31G>C (chr2-10043686-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003597.5(KLF11):c.-31G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000673 in 148,670 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLF11
NM_003597.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.763

Publications

0 publications found

Variant links:

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

KLF11 links:

ENSG00000260077 (HGNC:):

ENSG00000260077 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003597.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	NM_003597.5	MANE Select	c.-31G>C		5_prime_UTR	Exon 1 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.-211G>C		upstream_gene	N/A	NP_001171187.1	O14901-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLF11	ENST00000305883.6	TSL:1 MANE Select	c.-31G>C	5_prime_UTR	Exon 1 of 4	ENSP00000307023.1	O14901-1
KLF11	ENST00000921466.1		c.-31G>C	5_prime_UTR	Exon 1 of 3	ENSP00000591525.1
KLF11	ENST00000401510.5	TSL:3	c.-10+615G>C	intron	N/A	ENSP00000386058.1	B5MCC4

Frequencies

GnomAD3 genomes

AF:

0.00000673

AC:

AN:

148670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1154406

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

568892

African (AFR)

AF:

0.00

AC:

AN:

21974

American (AMR)

AF:

0.00

AC:

AN:

23346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16906

East Asian (EAS)

AF:

0.00

AC:

AN:

15518

South Asian (SAS)

AF:

0.00

AC:

AN:

68644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2982

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

940234

Other (OTH)

AF:

0.00

AC:

AN:

42898

GnomAD4 genome

AF:

0.00000673

AC:

AN:

148670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72428

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41098

American (AMR)

AF:

0.00

AC:

AN:

14986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3408

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66686

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.76

PromoterAI

-0.068

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over