rs4444493

Variant names:

• chr2-10053051-C-A
• rs4444493
• NM_003597.5:c.*544C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-10053051-C-A
• chr2-10053051-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003597.5(KLF11):​c.*544C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 392,436 control chromosomes in the GnomAD database, including 2,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (680 hom., cov: 33)
  • Exomes 𝑓: 0.10 (1450 hom.)
• Consequence: KLF11 NM_003597.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.558
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-10053051-C-A is Benign according to our data. Variant chr2-10053051-C-A is described in ClinVar as Benign. ClinVar VariationId is 330654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

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.*544C>A		3_prime_UTR	Exon 4 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.*544C>A		3_prime_UTR	Exon 4 of 4	NP_001171187.1	O14901-2
	KLF11	NM_001177718.2		c.*544C>A		3_prime_UTR	Exon 4 of 4	NP_001171189.1	O14901-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.*544C>A		3_prime_UTR	Exon 4 of 4	ENSP00000307023.1	O14901-1
	KLF11	ENST00000535335.1	TSL:2	c.*544C>A		3_prime_UTR	Exon 4 of 4	ENSP00000442722.1	O14901-2
	KLF11	ENST00000540845.5	TSL:2	c.*544C>A		3_prime_UTR	Exon 4 of 4	ENSP00000444690.1	O14901-2

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12748 AN: 152120 Hom.: 680 Cov.: 33

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0986

GnomAD4 exome AF: 0.100 AC: 24105 AN: 240198 Hom.: 1450 Cov.: 0 AF XY: 0.101 AC XY: 12357 AN XY: 121834

African (AFR) AF: 0.0346 AC: 243 AN: 7028

American (AMR) AF: 0.0789 AC: 578 AN: 7328

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 1266 AN: 9040

East Asian (EAS) AF: 0.00 AC: 0 AN: 22442

South Asian (SAS) AF: 0.0709 AC: 155 AN: 2186

European-Finnish (FIN) AF: 0.0770 AC: 1542 AN: 20026

Middle Eastern (MID) AF: 0.136 AC: 170 AN: 1248

European-Non Finnish (NFE) AF: 0.120 AC: 18597 AN: 154924

Other (OTH) AF: 0.0973 AC: 1554 AN: 15976

GnomAD4 genome AF: 0.0837 AC: 12749 AN: 152238 Hom.: 680 Cov.: 33 AF XY: 0.0808 AC XY: 6016 AN XY: 74416

African (AFR) AF: 0.0330 AC: 1370 AN: 41550

American (AMR) AF: 0.0875 AC: 1339 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0624 AC: 301 AN: 4824

European-Finnish (FIN) AF: 0.0688 AC: 728 AN: 10586

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8081 AN: 68012

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.113 Hom.: 1451

Bravo AF: 0.0842

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity-onset diabetes of the young type 7 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.67
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4444493; hg19: chr2-10193178;