rs6413441

Variant names:

• chr7-45915651-AT-A
• rs6413441
• NM_000598.5:c.751-707delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000598.5(IGFBP3):​c.751-707delA 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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000598.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	NM_000598.5	MANE Select	c.751-707delA		intron	N/A	NP_000589.2	P17936-1
	IGFBP3	NM_001013398.2		c.769-707delA		intron	N/A	NP_001013416.1	P17936-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.751-707delA		intron	N/A	ENSP00000477772.2	P17936-1
	IGFBP3	ENST00000908406.1		c.841-707delA		intron	N/A	ENSP00000578465.1
	IGFBP3	ENST00000381083.9	TSL:5	c.769-707delA		intron	N/A	ENSP00000370473.4	P17936-2

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

African (AFR) AF: 0.619 AC: 25684 AN: 41462

American (AMR) AF: 0.439 AC: 6706 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2191 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3801 AN: 5154

South Asian (SAS) AF: 0.484 AC: 2332 AN: 4814

European-Finnish (FIN) AF: 0.509 AC: 5371 AN: 10554

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.578 AC: 39300 AN: 67958

Other (OTH) AF: 0.548 AC: 1154 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.43
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6413441; hg19: chr7-45955250;