chr7-45920349-TC-T

Variant names:

• chr7-45920349-TC-T
• rs11292609
• NM_000598.5:c.403+388delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000598.5(IGFBP3):​c.403+388delG 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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.403+388delG		intron_variant	Intron 1 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.421+370delG		intron_variant	Intron 1 of 4		NP_001013416.1
IGFBP3	XM_047420325.1	c.403+388delG		intron_variant	Intron 1 of 3		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.403+388delG		intron_variant	Intron 1 of 4	5	NM_000598.5	ENSP00000477772.2

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

African (AFR) AF: 0.762 AC: 2045 AN: 2684

American (AMR) AF: 0.822 AC: 1587 AN: 1930

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2067 AN: 2874

East Asian (EAS) AF: 0.981 AC: 5312 AN: 5414

South Asian (SAS) AF: 0.695 AC: 452 AN: 650

European-Finnish (FIN) AF: 0.853 AC: 3763 AN: 4414

Middle Eastern (MID) AF: 0.637 AC: 269 AN: 422

European-Non Finnish (NFE) AF: 0.798 AC: 36102 AN: 45242

Other (OTH) AF: 0.788 AC: 3835 AN: 4868

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

African (AFR) AF: 0.761 AC: 31459 AN: 41344

American (AMR) AF: 0.824 AC: 12582 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2611 AN: 3468

East Asian (EAS) AF: 0.967 AC: 4955 AN: 5124

South Asian (SAS) AF: 0.707 AC: 3389 AN: 4796

European-Finnish (FIN) AF: 0.876 AC: 9251 AN: 10566

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55028 AN: 67962

Other (OTH) AF: 0.767 AC: 1614 AN: 2104

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11292609; hg19: chr7-45959948;