7-45921946-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000448817.1	TSL:4	c.-247A>G		upstream_gene	N/A	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

African (AFR) AF: 0.948 AC: 110 AN: 116

American (AMR) AF: 0.455 AC: 70 AN: 154

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 207 AN: 228

East Asian (EAS) AF: 0.883 AC: 53 AN: 60

South Asian (SAS) AF: 0.779 AC: 1922 AN: 2466

European-Finnish (FIN) AF: 0.609 AC: 572 AN: 940

Middle Eastern (MID) AF: 0.850 AC: 34 AN: 40

European-Non Finnish (NFE) AF: 0.755 AC: 4706 AN: 6232

Other (OTH) AF: 0.773 AC: 456 AN: 590

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

African (AFR) AF: 0.908 AC: 37749 AN: 41576

American (AMR) AF: 0.627 AC: 9583 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 3004 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4067 AN: 5168

South Asian (SAS) AF: 0.778 AC: 3752 AN: 4820

European-Finnish (FIN) AF: 0.636 AC: 6734 AN: 10594

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52938 AN: 68034

Other (OTH) AF: 0.799 AC: 1691 AN: 2116

Alfa AF: 0.808 Hom.: 7958

Bravo AF: 0.793

Asia WGS AF: 0.771 AC: 2682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.2
DANN	Benign	0.29
PhyloP100		-0.26
PromoterAI		-0.0082	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2132572; hg19: chr7-45961545;