rs2284932

Variant names:

• chr2-207147785-G-A
• rs2284932
• NM_003709.4:c.102+17682C>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.102+17682C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,100 control chromosomes in the GnomAD database, including 9,698 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 0.34 (9698 hom., cov: 32)
• Consequence: KLF7 NM_003709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF7	NM_003709.4	c.102+17682C>T		intron_variant	Intron 1 of 3	ENST00000309446.11	NP_003700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF7	ENST00000309446.11	c.102+17682C>T		intron_variant	Intron 1 of 3	1	NM_003709.4	ENSP00000309570.6

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51191 AN: 151982 Hom.: 9699 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.337 AC: 51196 AN: 152100 Hom.: 9698 Cov.: 32 AF XY: 0.343 AC XY: 25514 AN XY: 74334

African (AFR) AF: 0.172 AC: 7144 AN: 41526

American (AMR) AF: 0.380 AC: 5814 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3470

East Asian (EAS) AF: 0.527 AC: 2717 AN: 5152

South Asian (SAS) AF: 0.395 AC: 1900 AN: 4814

European-Finnish (FIN) AF: 0.498 AC: 5257 AN: 10558

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26421 AN: 67972

Other (OTH) AF: 0.321 AC: 679 AN: 2112

Alfa AF: 0.378 Hom.: 6647

Bravo AF: 0.321

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.73
PhyloP100		-1.2
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: rs2284932; hg19: chr2-208012509;