rs2132571

Variant names:

• chr7-45922075-T-C
• rs2132571
• ENST00000448817.1:c.-376A>G

Variant summary

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

The ENST00000448817.1(IGFBP3):​c.-376A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,252 control chromosomes in the GnomAD database, including 38,919 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 0.71 (38919 hom., cov: 35)
• Consequence: IGFBP3 ENST00000448817.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448817.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000448817.1	TSL:4	c.-376A>G		upstream_gene	N/A	ENSP00000389668.1	C9JMX4

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108360 AN: 152134 Hom.: 38905 Cov.: 35

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.712 AC: 108423 AN: 152252 Hom.: 38919 Cov.: 35 AF XY: 0.716 AC XY: 53314 AN XY: 74436

African (AFR) AF: 0.722 AC: 29997 AN: 41536

American (AMR) AF: 0.760 AC: 11627 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2255 AN: 3472

East Asian (EAS) AF: 0.966 AC: 5010 AN: 5186

South Asian (SAS) AF: 0.668 AC: 3219 AN: 4820

European-Finnish (FIN) AF: 0.745 AC: 7900 AN: 10606

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46054 AN: 68012

Other (OTH) AF: 0.692 AC: 1462 AN: 2114

Alfa AF: 0.688 Hom.: 6572

Bravo AF: 0.718

Asia WGS AF: 0.779 AC: 2707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		-1.2
PromoterAI		0.069	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2132571; hg19: chr7-45961674;