Genetic Variant IGFBP1:c.520-134C>T (chr7-45891798-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000596.4(IGFBP1):c.520-134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 746,476 control chromosomes in the GnomAD database, including 98 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 0.016 ( 70 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 28 hom. )

Consequence

IGFBP1
NM_000596.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.593

Publications

1 publications found

Variant links:

Genes affected

IGFBP1 (HGNC:5469): (insulin like growth factor binding protein 1) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP N-terminal domain and a thyroglobulin type-I domain. The encoded protein, mainly expressed in the liver, circulates in the plasma and binds both insulin-like growth factors (IGFs) I and II, prolonging their half-lives and altering their interaction with cell surface receptors. This protein is important in cell migration and metabolism. Low levels of this protein may be associated with impaired glucose tolerance, vascular disease and hypertension in human patients. [provided by RefSeq, Aug 2017]

IGFBP1 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP1	NM_000596.4 link	c.520-134C>T		intron_variant	Intron 2 of 3	ENST00000275525.8	NP_000587.1	P08833

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGFBP1	ENST00000275525.8 link	c.520-134C>T	intron_variant	Intron 2 of 3	1	NM_000596.4	ENSP00000275525.3	P08833
IGFBP1	ENST00000457280.5 link	c.520-134C>T	intron_variant	Intron 2 of 3	5		ENSP00000413511.1	C9JXF9
IGFBP1	ENST00000468955.1 link	c.519+1081C>T	intron_variant	Intron 2 of 2	5		ENSP00000417069.1	C9J6H2

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2476

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.00183

AC:

1085

AN:

594132

Hom.:

AF XY:

0.00149

AC XY:

460

AN XY:

308636

show subpopulations

African (AFR)

AF:

0.0570

AC:

848

AN:

14880

American (AMR)

AF:

0.00393

AC:

AN:

20586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14812

East Asian (EAS)

AF:

0.00

AC:

AN:

32048

South Asian (SAS)

AF:

0.000166

AC:

AN:

48056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35262

Middle Eastern (MID)

AF:

0.00307

AC:

AN:

2606

European-Non Finnish (NFE)

AF:

0.0000683

AC:

AN:

395088

Other (OTH)

AF:

0.00367

AC:

113

AN:

30794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0163

AC:

2481

AN:

152344

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1156

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0567

AC:

2355

AN:

41570

American (AMR)

AF:

0.00601

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68028

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

108

217

325

434

542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0130

Hom.:

Bravo

AF:

0.0191

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.84

(source)

DANN

Benign

0.78

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism

(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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7-45891798-C-T

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