2-207088682-T-G

Position:

• chr2-207088682-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003709.4(KLF7):​c.734-101A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,295,624 control chromosomes in the GnomAD database, including 5,790 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 0.076 (577 hom., cov: 32)
  • Exomes 𝑓: 0.094 (5213 hom.)
• Consequence: KLF7 NM_003709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF7	NM_003709.4	c.734-101A>C		intron_variant		ENST00000309446.11	NP_003700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF7	ENST00000309446.11	c.734-101A>C		intron_variant		1	NM_003709.4	ENSP00000309570.6

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11557 AN: 152114 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0729

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0799

GnomAD4 exome AF: 0.0942 AC: 107673 AN: 1143394 Hom.: 5213 AF XY: 0.0928 AC XY: 52273 AN XY: 563134

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.0676

Gnomad4 ASJ exome AF: 0.0995

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0341

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.0988

Gnomad4 OTH exome AF: 0.0878

GnomAD4 genome AF: 0.0760 AC: 11562 AN: 152230 Hom.: 577 Cov.: 32 AF XY: 0.0772 AC XY: 5744 AN XY: 74426

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0727

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0588 Hom.: 84

Bravo AF: 0.0677

Asia WGS AF: 0.0710 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.9
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs2302870; hg19: chr2-207953406; COSMIC: COSV58742810;