rs4988515

chr7-45893001-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000596.4(IGFBP1):c.690C>T(p.Cys230=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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]

ACMG classification

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	UniProt
IGFBP1	NM_000596.4	c.690C>T	p.Cys230=	synonymous_variant	4/4	ENST00000275525.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP1	ENST00000275525.8	c.690C>T	p.Cys230=	synonymous_variant	4/4	1	NM_000596.4	P4
IGFBP1	ENST00000457280.5	c.684C>T	p.Cys228=	synonymous_variant	4/4	5		A2
IGFBP1	ENST00000468955.1	c.561C>T	p.Cys187=	synonymous_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12746 AN: 152088 Hom.: 899 Cov.: 33

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

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.: 29 AF XY: 0.0503 AC XY: 36530 AN XY: 726282

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.: 33 AF XY: 0.0815 AC XY: 6061 AN XY: 74412

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

Other links and lift over

dbSNP: rs4988515; hg19: chr7-45932600;