rs6743779

Variant names:

• chr2-207125314-A-C
• rs6743779
• NM_003709.4:c.103-910T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003709.4(KLF7):​c.103-910T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,098 control chromosomes in the GnomAD database, including 6,445 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 0.28 (6445 hom., cov: 32)
• Consequence: KLF7 NM_003709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 6 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 (AMR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF7	NM_003709.4	c.103-910T>G		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.103-910T>G		intron_variant	Intron 1 of 3	1	NM_003709.4	ENSP00000309570.6

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42284 AN: 151980 Hom.: 6448 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.278 AC: 42299 AN: 152098 Hom.: 6445 Cov.: 32 AF XY: 0.281 AC XY: 20900 AN XY: 74340

African (AFR) AF: 0.169 AC: 7027 AN: 41492

American (AMR) AF: 0.404 AC: 6181 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3472

East Asian (EAS) AF: 0.119 AC: 618 AN: 5178

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4818

European-Finnish (FIN) AF: 0.323 AC: 3414 AN: 10564

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21745 AN: 67974

Other (OTH) AF: 0.311 AC: 656 AN: 2112

Alfa AF: 0.309 Hom.: 7155

Bravo AF: 0.283

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		1.9
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: rs6743779; hg19: chr2-207990038;