rs11292609

Positions:

• chr7-45920349-TC-T
• chr7-45920349-TC-TCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000598.5(IGFBP3):​c.403+388del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (49083 hom., cov: 0)
  • Exomes 𝑓: 0.81 (22761 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP3	NM_000598.5	c.403+388del		intron_variant		ENST00000613132.5
IGFBP3	NM_001013398.2	c.421+370del		intron_variant
IGFBP3	XM_047420325.1	c.403+388del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP3	ENST00000613132.5	c.403+388del		intron_variant		5	NM_000598.5	P4

Frequencies

GnomAD3 genomes AF: 0.803 AC: 121787 AN: 151720 Hom.: 49053 Cov.: 0

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.774

GnomAD4 exome AF: 0.809 AC: 55432 AN: 68498 Hom.: 22761 Cov.: 0 AF XY: 0.807 AC XY: 27757 AN XY: 34376

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.822

Gnomad4 ASJ exome AF: 0.719

Gnomad4 EAS exome AF: 0.981

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.853

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.788

GnomAD4 genome AF: 0.803 AC: 121868 AN: 151838 Hom.: 49083 Cov.: 0 AF XY: 0.805 AC XY: 59762 AN XY: 74202

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.767

Alfa AF: 0.755 Hom.: 2214

Bravo AF: 0.798

Asia WGS AF: 0.799 AC: 2776 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11292609; hg19: chr7-45959948;