rs1263623

Variant names:

• chr2-207117057-T-C
• rs1263623
• NM_003709.4:c.733+6717A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

KLF7 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KLF7	NM_003709.4	c.733+6717A>G		intron_variant	Intron 2 of 3	ENST00000309446.11	NP_003700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF7	ENST00000309446.11	c.733+6717A>G		intron_variant	Intron 2 of 3	1	NM_003709.4	ENSP00000309570.6

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

African (AFR) AF: 0.229 AC: 9460 AN: 41294

American (AMR) AF: 0.105 AC: 1605 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3472

East Asian (EAS) AF: 0.344 AC: 1780 AN: 5178

South Asian (SAS) AF: 0.289 AC: 1395 AN: 4828

European-Finnish (FIN) AF: 0.155 AC: 1642 AN: 10594

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11894 AN: 67994

Other (OTH) AF: 0.168 AC: 355 AN: 2114

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
PhyloP100		-0.58
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: rs1263623; hg19: chr2-207981781;