Variant 7-45890586-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000596.4(IGFBP1):c.388A>C(p.Thr130Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

IGFBP1
NM_000596.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24586025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP1	NM_000596.4 linkuse as main transcript	c.388A>C	p.Thr130Pro	missense_variant	2/4	ENST00000275525.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IGFBP1	ENST00000275525.8 linkuse as main transcript	c.388A>C	p.Thr130Pro	missense_variant	2/4	1	NM_000596.4	P4
IGFBP1	ENST00000457280.5 linkuse as main transcript	c.388A>C	p.Thr130Pro	missense_variant	2/4	5		A2
IGFBP1	ENST00000468955.1 linkuse as main transcript	c.388A>C	p.Thr130Pro	missense_variant	2/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250796

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461220

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.388A>C (p.T130P) alteration is located in exon 2 (coding exon 2) of the IGFBP1 gene. This alteration results from a A to C substitution at nucleotide position 388, causing the threonine (T) at amino acid position 130 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.10

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.10

T;T;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.28

MutPred

0.27

Loss of phosphorylation at T130 (P = 0.0413);Loss of phosphorylation at T130 (P = 0.0413);Loss of phosphorylation at T130 (P = 0.0413);

MVP

0.54

MPC

0.55

ClinPred

0.36

GERP RS

3.8

Varity_R

0.15

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over