dbSNP rs2854747: IGFBP3:c.403+420C>T (chr7-45920318-G-A) – 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.403+420C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 192,158 control chromosomes in the GnomAD database, including 33,418 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 0.59 ( 26248 hom., cov: 31)

Exomes 𝑓: 0.58 ( 7170 hom. )

Consequence

IGFBP3
NM_000598.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.407

Publications

9 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:

Genome browser will be placed here

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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5 link	c.403+420C>T	intron_variant	Intron 1 of 4	ENST00000613132.5	NP_000589.2	P17936-1B3KPF0
IGFBP3	NM_001013398.2 link	c.421+402C>T	intron_variant	Intron 1 of 4		NP_001013416.1	P17936-2
IGFBP3	XM_047420325.1 link	c.403+420C>T	intron_variant	Intron 1 of 3		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5 link	c.403+420C>T		intron_variant	Intron 1 of 4	5	NM_000598.5	ENSP00000477772.2		P17936-1A6XND0

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

88727

AN:

151104

Hom.:

26245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.691

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.589

Gnomad OTH

AF:

0.560

GnomAD4 exome

AF:

0.582

AC:

23820

AN:

40938

Hom.:

7170

Cov.:

AF XY:

0.583

AC XY:

11989

AN XY:

20560

show subpopulations

African (AFR)

AF:

0.606

AC:

1039

AN:

1714

American (AMR)

AF:

0.401

AC:

457

AN:

1140

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

1035

AN:

1768

East Asian (EAS)

AF:

0.766

AC:

2127

AN:

2776

South Asian (SAS)

AF:

0.478

AC:

194

AN:

406

European-Finnish (FIN)

AF:

0.485

AC:

1145

AN:

2360

Middle Eastern (MID)

AF:

0.519

AC:

139

AN:

268

European-Non Finnish (NFE)

AF:

0.582

AC:

16032

AN:

27566

Other (OTH)

AF:

0.562

AC:

1652

AN:

2940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

470

940

1411

1881

2351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.587

AC:

88763

AN:

151220

Hom.:

26248

Cov.:

AF XY:

0.581

AC XY:

42847

AN XY:

73802

show subpopulations

African (AFR)

AF:

0.636

AC:

26274

AN:

41290

American (AMR)

AF:

0.451

AC:

6781

AN:

15022

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2145

AN:

3468

East Asian (EAS)

AF:

0.760

AC:

3886

AN:

5112

South Asian (SAS)

AF:

0.492

AC:

2361

AN:

4794

European-Finnish (FIN)

AF:

0.518

AC:

5376

AN:

10384

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.589

AC:

39981

AN:

67858

Other (OTH)

AF:

0.555

AC:

1162

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1863

3726

5589

7452

9315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.586

Hom.:

5610

Bravo

AF:

0.583

Asia WGS

AF:

0.565

AC:

1965

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.78

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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