rs2359965

Variant names:

• chr2-207116198-C-G
• rs2359965
• NM_003709.4:c.733+7576G>C

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+7576G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,112 control chromosomes in the GnomAD database, including 2,658 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 0.18 (2658 hom., cov: 32)
• Consequence: KLF7 NM_003709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003709.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF7	NM_003709.4	MANE Select	c.733+7576G>C		intron	N/A	NP_003700.1
	KLF7	NM_001270944.2		c.649+7576G>C		intron	N/A	NP_001257873.1
	KLF7	NM_001270943.2		c.634+7576G>C		intron	N/A	NP_001257872.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF7	ENST00000309446.11	TSL:1 MANE Select	c.733+7576G>C		intron	N/A	ENSP00000309570.6
	KLF7	ENST00000421199.5	TSL:1	c.634+7576G>C		intron	N/A	ENSP00000387510.1
	KLF7	ENST00000423015.5	TSL:1	c.531+7778G>C		intron	N/A	ENSP00000398572.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27384 AN: 151994 Hom.: 2659 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.180 AC: 27389 AN: 152112 Hom.: 2658 Cov.: 32 AF XY: 0.181 AC XY: 13443 AN XY: 74348

African (AFR) AF: 0.198 AC: 8225 AN: 41488

American (AMR) AF: 0.101 AC: 1546 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1661 AN: 5146

South Asian (SAS) AF: 0.282 AC: 1362 AN: 4826

European-Finnish (FIN) AF: 0.155 AC: 1646 AN: 10588

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11852 AN: 67980

Other (OTH) AF: 0.158 AC: 334 AN: 2112

Alfa AF: 0.170 Hom.: 289

Bravo AF: 0.173

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.4
DANN	Benign	0.55
PhyloP100		0.0030
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: rs2359965; hg19: chr2-207980922;