ENST00000448817.1:c.-247A>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000448817.1(IGFBP3):​c.-247A>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000448817.1	TSL:4	c.-247A>T		upstream_gene	N/A	ENSP00000389668.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 10856 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6126

African (AFR) AF: 0.00 AC: 0 AN: 116

American (AMR) AF: 0.00 AC: 0 AN: 154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 230

East Asian (EAS) AF: 0.00 AC: 0 AN: 60

South Asian (SAS) AF: 0.00 AC: 0 AN: 2468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 40

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6252

Other (OTH) AF: 0.00 AC: 0 AN: 592

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.46
PhyloP100		-0.26
PromoterAI		0.0074	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;