dbSNP rs35440925: IGFBP3:c.751-429C>G (chr7-45915374-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000598.5(IGFBP3):c.751-429C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 175,574 control chromosomes in the GnomAD database, including 3,069 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 0.18 ( 2614 hom., cov: 33)

Exomes 𝑓: 0.19 ( 455 hom. )

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
IGFBP3	NM_000598.5 link	c.751-429C>G	intron_variant	Intron 3 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2 link	c.769-429C>G	intron_variant	Intron 3 of 4		NP_001013416.1
IGFBP3	XM_047420325.1 link	c.751-429C>G	intron_variant	Intron 3 of 3		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5 link	c.751-429C>G		intron_variant	Intron 3 of 4	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27518

AN:

152036

Hom.:

2609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.0323

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.187

AC:

4382

AN:

23420

Hom.:

455

Cov.:

AF XY:

0.194

AC XY:

2292

AN XY:

11814

show subpopulations

African (AFR)

AF:

0.175

AC:

100

AN:

572

American (AMR)

AF:

0.160

AC:

194

AN:

1214

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

150

AN:

670

East Asian (EAS)

AF:

0.0273

AC:

AN:

1134

South Asian (SAS)

AF:

0.291

AC:

452

AN:

1554

European-Finnish (FIN)

AF:

0.129

AC:

175

AN:

1352

Middle Eastern (MID)

AF:

0.278

AC:

AN:

108

European-Non Finnish (NFE)

AF:

0.192

AC:

2966

AN:

15410

Other (OTH)

AF:

0.202

AC:

284

AN:

1406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

194

388

582

776

970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.181

AC:

27551

AN:

152154

Hom.:

2614

Cov.:

AF XY:

0.178

AC XY:

13260

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.169

AC:

6997

AN:

41490

American (AMR)

AF:

0.172

AC:

2629

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

812

AN:

3468

East Asian (EAS)

AF:

0.0323

AC:

167

AN:

5166

South Asian (SAS)

AF:

0.287

AC:

1384

AN:

4818

European-Finnish (FIN)

AF:

0.126

AC:

1336

AN:

10598

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13531

AN:

68000

Other (OTH)

AF:

0.218

AC:

460

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1156

2312

3468

4624

5780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0870

Hom.:

104

Bravo

AF:

0.180

Asia WGS

AF:

0.193

AC:

674

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

(source)

DANN

Benign

0.41

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over