NM_000596.4:c.520-396T>C

Variant names:

• chr7-45891536-T-C
• rs2854843
• NM_000596.4:c.520-396T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000596.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP1	NM_000596.4	MANE Select	c.520-396T>C		intron	N/A	NP_000587.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP1	ENST00000275525.8	TSL:1 MANE Select	c.520-396T>C		intron	N/A	ENSP00000275525.3
	IGFBP1	ENST00000457280.5	TSL:5	c.520-396T>C		intron	N/A	ENSP00000413511.1
	IGFBP1	ENST00000468955.1	TSL:5	c.519+819T>C		intron	N/A	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

African (AFR) AF: 0.100 AC: 4171 AN: 41540

American (AMR) AF: 0.190 AC: 2902 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.333 AC: 1719 AN: 5168

South Asian (SAS) AF: 0.116 AC: 560 AN: 4832

European-Finnish (FIN) AF: 0.102 AC: 1079 AN: 10606

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11706 AN: 67990

Other (OTH) AF: 0.183 AC: 387 AN: 2114

Alfa AF: 0.159 Hom.: 2067

Bravo AF: 0.160

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.79
DANN	Benign	0.54
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2854843; hg19: chr7-45931135;