chr7-45915430-A-T

Variant names:

• chr7-45915430-A-T
• rs3110697
• NM_000598.5:c.751-485T>A

Variant summary

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

The NM_000598.5(IGFBP3):​c.751-485T>A variant causes a intron 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 69 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=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000598.5. 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
	IGFBP3	NM_000598.5	MANE Select	c.751-485T>A		intron	N/A	NP_000589.2	P17936-1
	IGFBP3	NM_001013398.2		c.769-485T>A		intron	N/A	NP_001013416.1	P17936-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.751-485T>A		intron	N/A	ENSP00000477772.2	P17936-1
	IGFBP3	ENST00000908406.1		c.841-485T>A		intron	N/A	ENSP00000578465.1
	IGFBP3	ENST00000381083.9	TSL:5	c.769-485T>A		intron	N/A	ENSP00000370473.4	P17936-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14444 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 7396

African (AFR) AF: 0.00 AC: 0 AN: 306

American (AMR) AF: 0.00 AC: 0 AN: 812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 356

East Asian (EAS) AF: 0.00 AC: 0 AN: 824

South Asian (SAS) AF: 0.00 AC: 0 AN: 712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 9626

Other (OTH) AF: 0.00 AC: 0 AN: 822

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3110697; hg19: chr7-45955029;