dbSNP rs11765572: IGFBP3:p.Arg10* (chr7-45921672-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000448817.1(IGFBP3):c.28C>T(p.Arg10*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 453,732 control chromosomes in the GnomAD database, including 2,775 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 0.10 ( 908 hom., cov: 33)

Exomes 𝑓: 0.10 ( 1867 hom. )

Consequence

IGFBP3
ENST00000448817.1 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

6 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000448817.1 link	c.28C>T	p.Arg10*	stop_gained	Exon 1 of 3	4		ENSP00000389668.1		C9JMX4

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15406

AN:

152136

Hom.:

908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0745

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0679

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0475

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.0851

GnomAD2 exomes

AF:

0.0826

AC:

10616

AN:

128564

AF XY:

0.0830

show subpopulations

Gnomad AFR exome

AF:

0.0697

Gnomad AMR exome

AF:

0.0462

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.00102

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.0930

GnomAD4 exome

AF:

0.0999

AC:

30126

AN:

301478

Hom.:

1867

Cov.:

AF XY:

0.0967

AC XY:

16613

AN XY:

171790

show subpopulations

African (AFR)

AF:

0.0731

AC:

596

AN:

8148

American (AMR)

AF:

0.0470

AC:

1246

AN:

26532

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

1130

AN:

10714

East Asian (EAS)

AF:

0.000675

AC:

AN:

8894

South Asian (SAS)

AF:

0.0532

AC:

3104

AN:

58344

European-Finnish (FIN)

AF:

0.125

AC:

1635

AN:

13126

Middle Eastern (MID)

AF:

0.0605

AC:

168

AN:

2776

European-Non Finnish (NFE)

AF:

0.131

AC:

20801

AN:

158712

Other (OTH)

AF:

0.101

AC:

1440

AN:

14232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

1169

2338

3507

4676

5845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.101

AC:

15423

AN:

152254

Hom.:

908

Cov.:

AF XY:

0.0990

AC XY:

7369

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0747

AC:

3103

AN:

41558

American (AMR)

AF:

0.0678

AC:

1037

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

364

AN:

3468

East Asian (EAS)

AF:

0.00212

AC:

AN:

5180

South Asian (SAS)

AF:

0.0479

AC:

231

AN:

4822

European-Finnish (FIN)

AF:

0.130

AC:

1379

AN:

10612

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9038

AN:

67996

Other (OTH)

AF:

0.0842

AC:

178

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

723

1445

2168

2890

3613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.108

Hom.:

292

Bravo

AF:

0.0946

TwinsUK

AF:

0.130

AC:

482

ALSPAC

AF:

0.124

AC:

478

ExAC

AF:

0.0712

AC:

1348

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.18

(source)

DANN

Benign

0.95

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0067

PhyloP100

-2.0

GERP RS

-4.7

PromoterAI

-0.013

Neutral

(source)

Splicing

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