Genetic Variant IGFBP3:c.751-429C>A (chr7-45915374-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000598.5(IGFBP3):c.751-429C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IGFBP3
NM_000598.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.312

Publications

2 publications found

Variant links:

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]

IGFBP3 links:

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ACMG classification

Classification was made for transcript

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=-0.91).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	NM_000598.5	MANE Select	c.751-429C>A		intron	N/A	NP_000589.2
	IGFBP3	NM_001013398.2		c.769-429C>A		intron	N/A	NP_001013416.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.751-429C>A	intron	N/A	ENSP00000477772.2
IGFBP3	ENST00000381083.9	TSL:5	c.769-429C>A	intron	N/A	ENSP00000370473.4
IGFBP3	ENST00000381086.9	TSL:2	c.460-429C>A	intron	N/A	ENSP00000370476.4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

23496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11852

African (AFR)

AF:

0.00

AC:

AN:

572

American (AMR)

AF:

0.00

AC:

AN:

1214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

670

East Asian (EAS)

AF:

0.00

AC:

AN:

1134

South Asian (SAS)

AF:

0.00

AC:

AN:

1560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

108

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

15470

Other (OTH)

AF:

0.00

AC:

AN:

1416

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41380

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

(source)

DANN

Benign

0.52

PhyloP100

-0.31

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over