7-45891536-T-C

Position:

• chr7-45891536-T-C

Variant summary

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

The NM_000596.4(IGFBP1):​c.520-396T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,224 control chromosomes in the GnomAD database, including 2,041 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 0.15 (2041 hom., cov: 33)
• Consequence: IGFBP1 NM_000596.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP1	NM_000596.4	c.520-396T>C		intron_variant		ENST00000275525.8	NP_000587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP1	ENST00000275525.8	c.520-396T>C		intron_variant		1	NM_000596.4	ENSP00000275525.3
IGFBP1	ENST00000457280.5	c.520-396T>C		intron_variant		5		ENSP00000413511.1
IGFBP1	ENST00000468955.1	c.519+819T>C		intron_variant		5		ENSP00000417069.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23080 AN: 152102 Hom.: 2036 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.152 AC: 23086 AN: 152224 Hom.: 2041 Cov.: 33 AF XY: 0.151 AC XY: 11206 AN XY: 74428

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.183

Alfa AF: 0.160 Hom.: 1650

Bravo AF: 0.160

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.79
DANN	Benign	0.54

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: rs2854843; hg19: chr7-45931135;