rs1263623

Positions:

• chr2-207117057-T-C
• chr2-207117057-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003709.4(KLF7):​c.733+6717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,958 control chromosomes in the GnomAD database, including 2,993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2993 hom., cov: 32)
• Consequence: KLF7 NM_003709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576

Genes affected

KLF7 (HGNC:6350): (KLF transcription factor 7) The protein encoded by this gene is a member of the Kruppel-like transcriptional regulator family. Members in this family regulate cell proliferation, differentiation and survival and contain three C2H2 zinc fingers at the C-terminus that mediate binding to GC-rich sites. This protein may contribute to the progression of type 2 diabetes by inhibiting insulin expression and secretion in pancreatic beta-cells and by deregulating adipocytokine secretion in adipocytes. A pseudogene of this gene is located on the long arm of chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF7	NM_003709.4	c.733+6717A>G		intron_variant		ENST00000309446.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF7	ENST00000309446.11	c.733+6717A>G		intron_variant		1	NM_003709.4	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28894 AN: 151844 Hom.: 2992 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28900 AN: 151958 Hom.: 2993 Cov.: 32 AF XY: 0.191 AC XY: 14189 AN XY: 74300

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.168

Alfa AF: 0.177 Hom.: 306

Bravo AF: 0.184

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.65

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: rs1263623; hg19: chr2-207981781;