dbSNP rs35496550: IGFBP3:c.*772delA (chr7-45913077-CT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_000598.5(IGFBP3):c.*772delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 152,240 control chromosomes in the GnomAD database, including 682 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.084 ( 682 hom., cov: 31)

Exomes 𝑓: 0.038 ( 0 hom. )

Consequence

IGFBP3
NM_000598.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.04

Publications

3 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 = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5 link	c.*772delA		3_prime_UTR_variant	Exon 5 of 5	ENST00000613132.5	NP_000589.2	P17936-1B3KPF0
IGFBP3	NM_001013398.2 link	c.*772delA		3_prime_UTR_variant	Exon 5 of 5		NP_001013416.1	P17936-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGFBP3	ENST00000613132.5 link	c.*772delA	3_prime_UTR_variant	Exon 5 of 5	5	NM_000598.5	ENSP00000477772.2	P17936-1A6XND0
IGFBP3	ENST00000381083.9 link	c.*772delA	3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000370473.4	P17936-2
IGFBP3	ENST00000381086.9 link	c.*772delA	3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000370476.4	B3KWK7

Frequencies

GnomAD3 genomes

AF:

0.0840

AC:

12782

AN:

152094

Hom.:

679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.0900

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0383

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.0385

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0625

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0714

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0840

AC:

12782

AN:

152214

Hom.:

682

Cov.:

AF XY:

0.0799

AC XY:

5947

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0332

AC:

1379

AN:

41542

American (AMR)

AF:

0.0900

AC:

1376

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

361

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5168

South Asian (SAS)

AF:

0.0371

AC:

179

AN:

4820

European-Finnish (FIN)

AF:

0.0587

AC:

622

AN:

10602

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8489

AN:

67996

Other (OTH)

AF:

0.107

AC:

227

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

586

1173

1759

2346

2932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0194

Hom.:

Bravo

AF:

0.0847

Asia WGS

AF:

0.0380

AC:

134

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-3.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over