chr2-10043708-G-A

Variant names:

• chr2-10043708-G-A
• rs550497503
• NM_003597.5:c.-9G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003597.5(KLF11):​c.-9G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,354,350 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: KLF11 NM_003597.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.221
• Publications: 2 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

ENSG00000260077 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-10043708-G-A is Benign according to our data. Variant chr2-10043708-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 259093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 229 AD gene.

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.-9G>A		5_prime_UTR	Exon 1 of 4	NP_003588.1
	KLF11	NM_001177716.2		c.-189G>A		upstream_gene	N/A	NP_001171187.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.-9G>A		5_prime_UTR	Exon 1 of 4	ENSP00000307023.1
	KLF11	ENST00000921466.1		c.-9G>A		5_prime_UTR	Exon 1 of 3	ENSP00000591525.1
	KLF11	ENST00000401510.5	TSL:3	c.-10+637G>A		intron	N/A	ENSP00000386058.1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 229 AN: 148804 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000933

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: 0.0000150

Gnomad OTH AF: 0.000487

GnomAD2 exomes AF: 0.000146 AC: 13 AN: 89070 AF XY: 0.0000998

Gnomad AFR exome AF: 0.00512

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.000145

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000138 AC: 166 AN: 1205438 Hom.: 1 Cov.: 29 AF XY: 0.000129 AC XY: 77 AN XY: 594938

African (AFR) AF: 0.00623 AC: 144 AN: 23096

American (AMR) AF: 0.000265 AC: 7 AN: 26426

Ashkenazi Jewish (ASJ) AF: 0.0000542 AC: 1 AN: 18438

East Asian (EAS) AF: 0.00 AC: 0 AN: 19106

South Asian (SAS) AF: 0.00 AC: 0 AN: 72650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3360

European-Non Finnish (NFE) AF: 0.00000206 AC: 2 AN: 970556

Other (OTH) AF: 0.000261 AC: 12 AN: 46020

GnomAD4 genome AF: 0.00154 AC: 229 AN: 148912 Hom.: 1 Cov.: 33 AF XY: 0.00140 AC XY: 102 AN XY: 72610

African (AFR) AF: 0.00517 AC: 213 AN: 41208

American (AMR) AF: 0.000932 AC: 14 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66694

Other (OTH) AF: 0.000482 AC: 1 AN: 2076

Alfa AF: 0.00103 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.96
PhyloP100		-0.22
PromoterAI		-0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs550497503; hg19: chr2-10183835;