chr7-45915430-A-T

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_000598.5(IGFBP3):c.751-485T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene IGFBP3 is a tumor suppressor gene (CancerMine: 6 TSG, 6 oncogene citations). The gene IGFBP3 is a known oncogene (CancerMine: 6 TSG, 6 oncogene citations). The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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: 70 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]

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000598.5. You can select a different transcript below to see updated classification 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	Intron 3 of 4	Prot: NP_000589.2 UniProt:
	IGFBP3 NM_001013398.2		c.769-485T>A	intron	Intron 3 of 4	Prot: NP_001013416.1 UniProt:

IGFBP3 NM_000598.5

MANE Select

HGVSc / HGVSpc.751-485T>A

Exon rankIntron 3 of 4

intron

Prot: NP_000589.2UniProt: P17936-1

IGFBP3 NM_001013398.2

HGVSc / HGVSpc.769-485T>A

Exon rankIntron 3 of 4

intron

Prot: NP_001013416.1UniProt: P17936-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	IGFBP3 ENST00000613132.5	TSL:5MANE Select	c.751-485T>A	intron	Intron 3 of 4	Prot: ENSP00000477772.2 UniProt:
	IGFBP3 ENST00000908406.1		c.841-485T>A	intron	Intron 4 of 5	Prot: ENSP00000578465.1 UniProt:
	IGFBP3 ENST00000381083.9	TSL:5	c.769-485T>A	intron	Intron 3 of 4	Prot: ENSP00000370473.4 UniProt:

IGFBP3 ENST00000613132.5

TSL:5MANE Select

HGVSc / HGVSpc.751-485T>A

Exon rankIntron 3 of 4

intron

Prot: ENSP00000477772.2UniProt: P17936-1

IGFBP3 ENST00000908406.1

HGVSc / HGVSpc.841-485T>A

Exon rankIntron 4 of 5

intron

Prot: ENSP00000578465.1UniProt: A0ACI8RUV2

IGFBP3 ENST00000381083.9

TSL:5

HGVSc / HGVSpc.769-485T>A

Exon rankIntron 3 of 4

intron

Prot: ENSP00000370473.4UniProt: P17936-2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome Warning	AF: 0.00	AC:0	Hom:0	AN:14444	Cov:
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32
Local & regional cohorts 1 source Population-specific and national genomic databases
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.00000800	AC:1	Hom:0	AN:122804	Cov:

Showing 4 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.36
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.56
GPN-Star LLR	N/A	0.71
GPN-Star score	N/A	-0.71
PhyloP100	Benign	0.20

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3110697;

hg19: chr7-45955029;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar