rs2244166

Variant names:

• chr2-207116120-G-A
• rs2244166
• NM_003709.4:c.733+7654C>T

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+7654C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,162 control chromosomes in the GnomAD database, including 3,124 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 0.20 (3124 hom., cov: 32)
• Consequence: KLF7 NM_003709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF7	NM_003709.4	MANE Select	c.733+7654C>T		intron	N/A	NP_003700.1	O75840-1
	KLF7	NM_001270944.2		c.649+7654C>T		intron	N/A	NP_001257873.1	O75840-4
	KLF7	NM_001270943.2		c.634+7654C>T		intron	N/A	NP_001257872.1	O75840-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF7	ENST00000309446.11	TSL:1 MANE Select	c.733+7654C>T		intron	N/A	ENSP00000309570.6	O75840-1
	KLF7	ENST00000421199.5	TSL:1	c.634+7654C>T		intron	N/A	ENSP00000387510.1	O75840-2
	KLF7	ENST00000423015.5	TSL:1	c.531+7856C>T		intron	N/A	ENSP00000398572.1	O75840-3

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30010 AN: 152044 Hom.: 3127 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.197 AC: 30015 AN: 152162 Hom.: 3124 Cov.: 32 AF XY: 0.197 AC XY: 14677 AN XY: 74384

African (AFR) AF: 0.226 AC: 9381 AN: 41490

American (AMR) AF: 0.120 AC: 1839 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 681 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1584 AN: 5176

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4822

European-Finnish (FIN) AF: 0.159 AC: 1684 AN: 10600

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12799 AN: 67992

Other (OTH) AF: 0.182 AC: 383 AN: 2110

Alfa AF: 0.186 Hom.: 335

Bravo AF: 0.192

Asia WGS AF: 0.313 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		-0.14
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: rs2244166; hg19: chr2-207980844;