rs1038766626

Variant names:

• chr2-10043641-G-A
• rs1038766626
• NM_003597.5:c.-76G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_003597.5(KLF11):​c.-76G>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 0.00115 in 1,040,192 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (6 hom.)
• Consequence: KLF11 NM_003597.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.643
• Publications: 1 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]

ENSG00000260077 (HGNC:):

KLF11-DT (HGNC:56037): (KLF11 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00536 (789/147214) while in subpopulation AFR AF = 0.0179 (734/40984). AF 95% confidence interval is 0.0168. There are 9 homozygotes in GnomAd4. There are 377 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 789 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.-76G>A		5_prime_UTR	Exon 1 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.-256G>A		upstream_gene	N/A	NP_001171187.1	O14901-2
	KLF11-DT	NR_135558.1		n.-240C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.-76G>A		5_prime_UTR	Exon 1 of 4	ENSP00000307023.1	O14901-1
	KLF11	ENST00000921466.1		c.-76G>A		5_prime_UTR	Exon 1 of 3	ENSP00000591525.1
	KLF11	ENST00000401510.5	TSL:3	c.-10+570G>A		intron	N/A	ENSP00000386058.1	B5MCC4

Frequencies

GnomAD3 genomes AF: 0.00532 AC: 783 AN: 147106 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

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: 0.0000756

Gnomad OTH AF: 0.00793

GnomAD4 exome AF: 0.000459 AC: 410 AN: 892978 Hom.: 6 Cov.: 14 AF XY: 0.000445 AC XY: 191 AN XY: 429240

African (AFR) AF: 0.0221 AC: 367 AN: 16614

American (AMR) AF: 0.00131 AC: 6 AN: 4576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8512

East Asian (EAS) AF: 0.00 AC: 0 AN: 7504

South Asian (SAS) AF: 0.00 AC: 0 AN: 28486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7170

Middle Eastern (MID) AF: 0.00246 AC: 5 AN: 2030

European-Non Finnish (NFE) AF: 0.00000889 AC: 7 AN: 787340

Other (OTH) AF: 0.000813 AC: 25 AN: 30746

GnomAD4 genome AF: 0.00536 AC: 789 AN: 147214 Hom.: 9 Cov.: 32 AF XY: 0.00526 AC XY: 377 AN XY: 71714

African (AFR) AF: 0.0179 AC: 734 AN: 40984

American (AMR) AF: 0.00229 AC: 34 AN: 14838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8738

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

European-Non Finnish (NFE) AF: 0.0000756 AC: 5 AN: 66120

Other (OTH) AF: 0.00784 AC: 16 AN: 2040

Alfa AF: 0.00448 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Maturity-onset diabetes of the young type 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.64
PromoterAI		-0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=298/2	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: rs1038766626; hg19: chr2-10183768;