dbSNP rs6670: IGFBP3:c.*1195A>T (chr7-45912655-T-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.*1195A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,606 control chromosomes in the GnomAD database, including 2,946 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 ( 2937 hom., cov: 32)

Exomes 𝑓: 0.16 ( 9 hom. )

Consequence

IGFBP3
NM_000598.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.146

Publications

35 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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5 link	c.*1195A>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000613132.5	NP_000589.2	P17936-1B3KPF0
IGFBP3	NM_001013398.2 link	c.*1195A>T		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.*1195A>T	3_prime_UTR_variant	Exon 5 of 5	5	NM_000598.5	ENSP00000477772.2	P17936-1A6XND0
IGFBP3	ENST00000381083.9 link	c.*1195A>T	3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000370473.4	P17936-2
IGFBP3	ENST00000381086.9 link	c.*1195A>T	3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000370476.4	B3KWK7

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27877

AN:

152050

Hom.:

2938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.183

GnomAD4 exome

AF:

0.162

AC:

AN:

438

Hom.:

Cov.:

AF XY:

0.173

AC XY:

AN XY:

266

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:

0.162

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.183

AC:

27882

AN:

152168

Hom.:

2937

Cov.:

AF XY:

0.183

AC XY:

13579

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.122

AC:

5068

AN:

41502

American (AMR)

AF:

0.168

AC:

2571

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

911

AN:

3466

East Asian (EAS)

AF:

0.0212

AC:

110

AN:

5182

South Asian (SAS)

AF:

0.407

AC:

1959

AN:

4814

European-Finnish (FIN)

AF:

0.141

AC:

1499

AN:

10608

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14912

AN:

67990

Other (OTH)

AF:

0.185

AC:

390

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1131

2263

3394

4526

5657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.185

Hom.:

334

Bravo

AF:

0.176

Asia WGS

AF:

0.225

AC:

784

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

1.6

(source)

DANN

Benign

0.77

PhyloP100

0.15

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