rs35496550

Positions:

• chr7-45913077-CT-C

Variant summary

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

The NM_000598.5(IGFBP3):​c.*772del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 152,240 control chromosomes in the GnomAD database, including 682 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.084 (682 hom., cov: 31)
  • Exomes 𝑓: 0.038 (0 hom.)
• Consequence: IGFBP3 NM_000598.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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 (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.*772del		3_prime_UTR_variant	5/5	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.*772del		3_prime_UTR_variant	5/5		NP_001013416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.*772del		3_prime_UTR_variant	5/5	5	NM_000598.5	ENSP00000477772	P4
IGFBP3	ENST00000381083.9	c.*772del		3_prime_UTR_variant	5/5	5		ENSP00000370473	A1
IGFBP3	ENST00000381086.9	c.*772del		3_prime_UTR_variant	6/6	2		ENSP00000370476

Frequencies

GnomAD3 genomes AF: 0.0840 AC: 12782 AN: 152094 Hom.: 679 Cov.: 31

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0385 AC: 1 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0840 AC: 12782 AN: 152214 Hom.: 682 Cov.: 31 AF XY: 0.0799 AC XY: 5947 AN XY: 74414

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.0900

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0371

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0194 Hom.: 10

Bravo AF: 0.0847

Asia WGS AF: 0.0380 AC: 134 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: rs35496550; hg19: chr7-45952676;