rs3793345

Variant names:

• chr7-45918079-T-C
• rs3793345
• NM_000598.5:c.404-640A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000598.5(IGFBP3):​c.404-640A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,194 control chromosomes in the GnomAD database, including 2,995 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 0.19 (2995 hom., cov: 32)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.404-640A>G		intron_variant	Intron 1 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.422-640A>G		intron_variant	Intron 1 of 4		NP_001013416.1
IGFBP3	XM_047420325.1	c.404-640A>G		intron_variant	Intron 1 of 3		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.404-640A>G		intron_variant	Intron 1 of 4	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29478 AN: 152076 Hom.: 2987 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.194 AC: 29517 AN: 152194 Hom.: 2995 Cov.: 32 AF XY: 0.191 AC XY: 14194 AN XY: 74402

African (AFR) AF: 0.204 AC: 8490 AN: 41516

American (AMR) AF: 0.177 AC: 2707 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3470

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5184

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4820

European-Finnish (FIN) AF: 0.126 AC: 1331 AN: 10588

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13737 AN: 68004

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.202 Hom.: 783

Bravo AF: 0.195

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.35
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3793345; hg19: chr7-45957678;