rs550497503

chr2-10043708-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 259093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 229 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF11	NM_003597.5	c.-9G>A		5_prime_UTR_variant	1/4	ENST00000305883.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF11	ENST00000305883.6	c.-9G>A		5_prime_UTR_variant	1/4	1	NM_003597.5	A2
KLF11	ENST00000401510.5	c.-10+637G>A		intron_variant		3

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

GnomAD3 exomes AF: 0.000146 AC: 13 AN: 89070 Hom.: 0 AF XY: 0.0000998 AC XY: 5 AN XY: 50118

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 SAS 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

Gnomad4 AFR exome AF: 0.00623

Gnomad4 AMR exome AF: 0.000265

Gnomad4 ASJ exome AF: 0.0000542

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000206

Gnomad4 OTH exome AF: 0.000261

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

Gnomad4 AFR AF: 0.00517

Gnomad4 AMR AF: 0.000932

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000150

Gnomad4 OTH AF: 0.000482

Alfa AF: 0.00103 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.5
Dann	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs550497503; hg19: chr2-10183835;