7-45921946-T-C

Variant names:

• chr7-45921946-T-C
• rs2132572
• ENST00000448817.1:c.-247A>G

Variant summary

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

The ENST00000448817.1(IGFBP3):​c.-247A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 163,106 control chromosomes in the GnomAD database, including 51,610 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 0.79 (48487 hom., cov: 34)
  • Exomes 𝑓: 0.75 (3123 hom.)
• Consequence: IGFBP3 ENST00000448817.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

Genes affected

IGFBP3 (HGNC:5472): (insulin like growth factor binding protein 3) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000448817.1	c.-247A>G		upstream_gene_variant		4		ENSP00000389668.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120441 AN: 152162 Hom.: 48439 Cov.: 34

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.751 AC: 8130 AN: 10826 Hom.: 3123 AF XY: 0.762 AC XY: 4655 AN XY: 6110

Gnomad4 AFR exome AF: 0.948

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.908

Gnomad4 EAS exome AF: 0.883

Gnomad4 SAS exome AF: 0.779

Gnomad4 FIN exome AF: 0.609

Gnomad4 NFE exome AF: 0.755

Gnomad4 OTH exome AF: 0.773

GnomAD4 genome AF: 0.792 AC: 120540 AN: 152280 Hom.: 48487 Cov.: 34 AF XY: 0.782 AC XY: 58224 AN XY: 74438

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.799

Alfa AF: 0.804 Hom.: 7627

Bravo AF: 0.793

Asia WGS AF: 0.771 AC: 2682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.2
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2132572; hg19: chr7-45961545;