NM_003709.4:c.733+17152G>A

Variant names:

• chr2-207106622-C-T
• rs1263605
• NM_003709.4:c.733+17152G>A

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+17152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,938 control chromosomes in the GnomAD database, including 12,653 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 0.40 (12653 hom., cov: 31)
• Consequence: KLF7 NM_003709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• 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 (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF7	NM_003709.4	c.733+17152G>A		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+17152G>A		intron_variant	Intron 2 of 3	1	NM_003709.4	ENSP00000309570.6

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60441 AN: 151820 Hom.: 12639 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.398 AC: 60495 AN: 151938 Hom.: 12653 Cov.: 31 AF XY: 0.396 AC XY: 29436 AN XY: 74270

African (AFR) AF: 0.521 AC: 21565 AN: 41420

American (AMR) AF: 0.267 AC: 4074 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1116 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2397 AN: 5154

South Asian (SAS) AF: 0.383 AC: 1845 AN: 4814

European-Finnish (FIN) AF: 0.352 AC: 3720 AN: 10556

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24578 AN: 67936

Other (OTH) AF: 0.369 AC: 777 AN: 2104

Alfa AF: 0.362 Hom.: 1647

Bravo AF: 0.394

Asia WGS AF: 0.446 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.73
PhyloP100		0.27
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: rs1263605; hg19: chr2-207971346;