dbSNP rs1281918306: KLF11:p.Gly8Gly (chr2-10043740-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_003597.5(KLF11):c.24C>G(p.Gly8Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,233,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

KLF11
NM_003597.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.825

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 2-10043740-C-G is Benign according to our data. Variant chr2-10043740-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1337155.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.825 with no splicing effect.

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.24C>G	p.Gly8Gly	synonymous	Exon 1 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.-157C>G		upstream_gene	N/A	NP_001171187.1	O14901-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLF11	ENST00000305883.6	TSL:1 MANE Select	c.24C>G	p.Gly8Gly	synonymous	Exon 1 of 4	ENSP00000307023.1	O14901-1
KLF11	ENST00000921466.1		c.24C>G	p.Gly8Gly	synonymous	Exon 1 of 3	ENSP00000591525.1
KLF11	ENST00000401510.5	TSL:3	c.-10+669C>G		intron	N/A	ENSP00000386058.1	B5MCC4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000104

AC:

AN:

96292

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000290

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000162

AC:

AN:

1233638

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

608934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23922

American (AMR)

AF:

0.00

AC:

AN:

27998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19366

East Asian (EAS)

AF:

0.00

AC:

AN:

21966

South Asian (SAS)

AF:

0.0000135

AC:

AN:

73926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3670

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

986324

Other (OTH)

AF:

0.00

AC:

AN:

47780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.8

(source)

DANN

Benign

0.65

PhyloP100

-0.82

PromoterAI

-0.21

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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