2-207088682-T-G

Variant names:

• chr2-207088682-T-G
• rs2302870
• NM_003709.4:c.734-101A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0984 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF7	NM_003709.4	MANE Select	c.734-101A>C		intron	N/A	NP_003700.1
	KLF7	NM_001270944.2		c.650-101A>C		intron	N/A	NP_001257873.1
	KLF7	NM_001270943.2		c.635-101A>C		intron	N/A	NP_001257872.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF7	ENST00000309446.11	TSL:1 MANE Select	c.734-101A>C		intron	N/A	ENSP00000309570.6
	KLF7	ENST00000421199.5	TSL:1	c.635-101A>C		intron	N/A	ENSP00000387510.1
	KLF7	ENST00000423015.5	TSL:1	c.532-101A>C		intron	N/A	ENSP00000398572.1

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

African (AFR) AF: 0.0147 AC: 392 AN: 26612

American (AMR) AF: 0.0676 AC: 1890 AN: 27972

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 1790 AN: 17992

East Asian (EAS) AF: 0.101 AC: 3738 AN: 36940

South Asian (SAS) AF: 0.0341 AC: 1885 AN: 55224

European-Finnish (FIN) AF: 0.156 AC: 5405 AN: 34690

Middle Eastern (MID) AF: 0.0732 AC: 352 AN: 4806

European-Non Finnish (NFE) AF: 0.0988 AC: 88021 AN: 891318

Other (OTH) AF: 0.0878 AC: 4200 AN: 47840

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

African (AFR) AF: 0.0178 AC: 740 AN: 41566

American (AMR) AF: 0.0727 AC: 1112 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0960 AC: 333 AN: 3470

East Asian (EAS) AF: 0.101 AC: 525 AN: 5174

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1624 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6824 AN: 67992

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.9
DANN	Benign	0.81
PhyloP100		-0.15
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: rs2302870; hg19: chr2-207953406; COSMIC: COSV58742810;