rs867976048

Variant names:

• chr2-10043500-G-A
• rs867976048
• ENST00000401510.5:c.-10+429G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-10043500-G-A
• chr2-10043500-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000401510.5(KLF11):​c.-10+429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 149,568 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: KLF11 ENST00000401510.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.525
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-10043500-G-A is Benign according to our data. Variant chr2-10043500-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1317869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00576 (817/141946) while in subpopulation AFR AF = 0.0193 (763/39474). AF 95% confidence interval is 0.0182. There are 4 homozygotes in GnomAd4. There are 392 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 817 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000401510.5. 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.-217G>A		upstream_gene	N/A	NP_003588.1	O14901-1
	KLF11-DT	NR_135558.1		n.-99C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000401510.5	TSL:3	c.-10+429G>A		intron	N/A	ENSP00000386058.1	B5MCC4
	ENSG00000260077	ENST00000837794.1		n.97-724C>T		intron	N/A
	ENSG00000260077	ENST00000837795.1		n.85-496C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00577 AC: 818 AN: 141858 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00258

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: 0.0000466

Gnomad OTH AF: 0.00770

GnomAD4 exome AF: 0.000131 AC: 1 AN: 7622 Hom.: 0 AF XY: 0.000269 AC XY: 1 AN XY: 3712

African (AFR) AF: 0.00694 AC: 1 AN: 144

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 60

East Asian (EAS) AF: 0.00 AC: 0 AN: 32

South Asian (SAS) AF: 0.00 AC: 0 AN: 164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6948

Other (OTH) AF: 0.00 AC: 0 AN: 250

GnomAD4 genome AF: 0.00576 AC: 817 AN: 141946 Hom.: 4 Cov.: 31 AF XY: 0.00569 AC XY: 392 AN XY: 68952

African (AFR) AF: 0.0193 AC: 763 AN: 39474

American (AMR) AF: 0.00251 AC: 36 AN: 14344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3340

East Asian (EAS) AF: 0.00 AC: 0 AN: 4752

South Asian (SAS) AF: 0.00 AC: 0 AN: 4608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.0000466 AC: 3 AN: 64338

Other (OTH) AF: 0.00761 AC: 15 AN: 1970

Alfa AF: 0.00406 Hom.: 1

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.95
PhyloP100		0.53
PromoterAI		-0.012	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs867976048; hg19: chr2-10183627;