Variant chr7-45893001-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000596.4(IGFBP1):c.690C>T(p.Cys230Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 1,611,946 control chromosomes in the GnomAD database, including 3,364 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 0.084 ( 904 hom., cov: 33)

Exomes 𝑓: 0.051 ( 2460 hom. )

Consequence

IGFBP1
NM_000596.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.356

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP7

Synonymous conserved (PhyloP=-0.356 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP1	NM_000596.4 linkuse as main transcript	c.690C>T	p.Cys230Cys	synonymous_variant	4/4	ENST00000275525.8	NP_000587.1	P08833

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGFBP1	ENST00000275525.8 linkuse as main transcript	c.690C>T	p.Cys230Cys	synonymous_variant	4/4	1	NM_000596.4	ENSP00000275525.3	P08833
IGFBP1	ENST00000457280.5 linkuse as main transcript	c.684C>T	p.Cys228Cys	synonymous_variant	4/4	5		ENSP00000413511.1	C9JXF9
IGFBP1	ENST00000468955.1 linkuse as main transcript	c.561C>T	p.Cys187Cys	synonymous_variant	3/3	5		ENSP00000417069.1	C9J6H2

Frequencies

GnomAD3 genomes

AF:

0.0838

AC:

12746

AN:

152088

Hom.:

899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0662

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0409

Gnomad FIN

AF:

0.0557

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0464

Gnomad OTH

AF:

0.0626

GnomAD3 exomes

AF:

0.0617

AC:

15522

AN:

251394

Hom.:

773

AF XY:

0.0564

AC XY:

7664

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.00844

Gnomad EAS exome

AF:

0.00321

Gnomad SAS exome

AF:

0.0403

Gnomad FIN exome

AF:

0.0604

Gnomad NFE exome

AF:

0.0497

Gnomad OTH exome

AF:

0.0500

GnomAD4 exome

AF:

0.0514

AC:

75089

AN:

1459740

Hom.:

2460

Cov.:

AF XY:

0.0503

AC XY:

36530

AN XY:

726282

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.00846

Gnomad4 EAS exome

AF:

0.00270

Gnomad4 SAS exome

AF:

0.0422

Gnomad4 FIN exome

AF:

0.0605

Gnomad4 NFE exome

AF:

0.0485

Gnomad4 OTH exome

AF:

0.0483

GnomAD4 genome

AF:

0.0839

AC:

12774

AN:

152206

Hom.:

904

Cov.:

AF XY:

0.0815

AC XY:

6061

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.0669

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.0404

Gnomad4 FIN

AF:

0.0557

Gnomad4 NFE

AF:

0.0463

Gnomad4 OTH

AF:

0.0619

Alfa

AF:

0.0522

Hom.:

697

Bravo

AF:

0.0909

Asia WGS

AF:

0.0400

AC:

141

AN:

3478

EpiCase

AF:

0.0416

EpiControl

AF:

0.0414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.4

DANN

Benign

0.65

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over