2-207166591-G-T

Variant names:

• chr2-207166591-G-T
• rs7568369
• ENST00000421199.5:c.3+549C>A

Variant summary

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

The ENST00000421199.5(KLF7):​c.3+549C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 157,254 control chromosomes in the GnomAD database, including 11,970 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 0.38 (11564 hom., cov: 28)
  • Exomes 𝑓: 0.35 (406 hom.)
• Consequence: KLF7 ENST00000421199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• 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]

MYOSLID (HGNC:51821): (myocardin-induced smooth muscle lncRNA, inducer of differentiation)

MIR7845 (HGNC:50267): (microRNA 7845) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF7	NM_001270943.2	c.3+549C>A		intron_variant	Intron 1 of 3		NP_001257872.1
KLF7	NM_001270942.1	c.-139+166C>A		intron_variant	Intron 1 of 4		NP_001257871.1
KLF7	XM_047446144.1	c.-139+166C>A		intron_variant	Intron 1 of 4		XP_047302100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF7	ENST00000421199.5	c.3+549C>A		intron_variant	Intron 1 of 3	1		ENSP00000387510.1
KLF7	ENST00000423015.5	c.-139+166C>A		intron_variant	Intron 1 of 4	1		ENSP00000398572.1
KLF7	ENST00000703736.1	c.3+549C>A		intron_variant	Intron 2 of 2			ENSP00000515456.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 56912 AN: 150386 Hom.: 11549 Cov.: 28

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.400

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.346 AC: 2342 AN: 6760 Hom.: 406 Cov.: 4 AF XY: 0.339 AC XY: 1121 AN XY: 3308

African (AFR) AF: 0.555 AC: 81 AN: 146

American (AMR) AF: 0.167 AC: 2 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 17 AN: 50

East Asian (EAS) AF: 0.125 AC: 5 AN: 40

South Asian (SAS) AF: 0.354 AC: 51 AN: 144

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.333 AC: 4 AN: 12

European-Non Finnish (NFE) AF: 0.345 AC: 2116 AN: 6140

Other (OTH) AF: 0.306 AC: 66 AN: 216

GnomAD4 genome AF: 0.379 AC: 56967 AN: 150494 Hom.: 11564 Cov.: 28 AF XY: 0.373 AC XY: 27376 AN XY: 73492

African (AFR) AF: 0.514 AC: 20993 AN: 40880

American (AMR) AF: 0.298 AC: 4539 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1164 AN: 3460

East Asian (EAS) AF: 0.103 AC: 508 AN: 4948

South Asian (SAS) AF: 0.318 AC: 1520 AN: 4780

European-Finnish (FIN) AF: 0.333 AC: 3454 AN: 10366

Middle Eastern (MID) AF: 0.393 AC: 114 AN: 290

European-Non Finnish (NFE) AF: 0.346 AC: 23340 AN: 67522

Other (OTH) AF: 0.380 AC: 794 AN: 2092

Alfa AF: 0.366 Hom.: 1301

Bravo AF: 0.381

Asia WGS AF: 0.211 AC: 732 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.0
DANN	Benign	0.86
PhyloP100		-0.074
PromoterAI		-0.073	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7568369; hg19: chr2-208031315;