rs34091405

Variant names:

• chr7-45915080-AAC-A
• rs34091405
• NM_000598.5:c.751-137_751-136delGT

Your query was ambiguous. Multiple possible variants found:

• chr7-45915080-AAC-A
• chr7-45915080-AAC-AACAC

Variant summary

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

The NM_000598.5(IGFBP3):​c.751-137_751-136delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,052,314 control chromosomes in the GnomAD database, including 19,716 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2486 hom., cov: 29)
  • Exomes 𝑓: 0.18 (17230 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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 (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.751-137_751-136delGT		intron_variant	Intron 3 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.769-137_769-136delGT		intron_variant	Intron 3 of 4		NP_001013416.1
IGFBP3	XM_047420325.1	c.751-137_751-136delGT		intron_variant	Intron 3 of 3		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.751-137_751-136delGT		intron_variant	Intron 3 of 4	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26743 AN: 152056 Hom.: 2482 Cov.: 29

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.179 AC: 161488 AN: 900140 Hom.: 17230 AF XY: 0.185 AC XY: 84497 AN XY: 456346

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.176 AC: 26770 AN: 152174 Hom.: 2486 Cov.: 29 AF XY: 0.173 AC XY: 12861 AN XY: 74408

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.0315

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.212

Alfa AF: 0.185 Hom.: 320

Bravo AF: 0.174

Asia WGS AF: 0.190 AC: 661 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: rs34091405; hg19: chr7-45954679;