rs35751739

Positions:

• chr7-45913091-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000598.5(IGFBP3):​c.*759G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 152,210 control chromosomes in the GnomAD database, including 148 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 0.028 (148 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGFBP3 NM_000598.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0283 (4313/152210) while in subpopulation NFE AF= 0.0384 (2609/68012). AF 95% confidence interval is 0.0371. There are 148 homozygotes in gnomad4. There are 2301 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 148 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.*759G>A		3_prime_UTR_variant	5/5	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.*759G>A		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.*759G>A		3_prime_UTR_variant	5/5	5	NM_000598.5	ENSP00000477772.2
IGFBP3	ENST00000381083.9	c.*759G>A		3_prime_UTR_variant	5/5	5		ENSP00000370473.4
IGFBP3	ENST00000381086.9	c.*759G>A		3_prime_UTR_variant	6/6	2		ENSP00000370476.4

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4313 AN: 152092 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.00430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0384

Gnomad OTH AF: 0.0187

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0283 AC: 4313 AN: 152210 Hom.: 148 Cov.: 32 AF XY: 0.0309 AC XY: 2301 AN XY: 74416

Gnomad4 AFR AF: 0.00428

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00395

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0384

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0414 Hom.: 39

Bravo AF: 0.0181

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.63

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: rs35751739; hg19: chr7-45952690;