rs1874479

Positions:

• chr7-45892627-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000596.4(IGFBP1):​c.649-333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,286 control chromosomes in the GnomAD database, including 1,005 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 0.10 (1005 hom., cov: 33)
• Consequence: IGFBP1 NM_000596.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP1	NM_000596.4	c.649-333A>G		intron_variant		ENST00000275525.8	NP_000587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP1	ENST00000275525.8	c.649-333A>G		intron_variant		1	NM_000596.4	ENSP00000275525.3
IGFBP1	ENST00000457280.5	c.649-339A>G		intron_variant		5		ENSP00000413511.1
IGFBP1	ENST00000468955.1	c.520-333A>G		intron_variant		5		ENSP00000417069.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15771 AN: 152168 Hom.: 1007 Cov.: 33

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.122

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15768 AN: 152286 Hom.: 1005 Cov.: 33 AF XY: 0.103 AC XY: 7694 AN XY: 74458

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.0810

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.122

Alfa AF: 0.120 Hom.: 217

Bravo AF: 0.0958

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.35
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs1874479; hg19: chr7-45932226;