rs6413441

Positions:

• chr7-45915651-AT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000598.5(IGFBP3):​c.751-707del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25358 hom., cov: 0)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426

Genes affected

IGFBP3 (HGNC:5472): (insulin like growth factor binding protein 3) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.751-707del		intron_variant		ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.769-707del		intron_variant			NP_001013416.1
IGFBP3	XM_047420325.1	c.751-707del		intron_variant			XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.751-707del		intron_variant		5	NM_000598.5	ENSP00000477772	P4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87260 AN: 151874 Hom.: 25354 Cov.: 0

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.574 AC: 87302 AN: 151992 Hom.: 25358 Cov.: 0 AF XY: 0.568 AC XY: 42198 AN XY: 74280

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.548

Alfa AF: 0.361 Hom.: 708

Bravo AF: 0.572

Asia WGS AF: 0.557 AC: 1938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs6413441; hg19: chr7-45955250;