Variant rs2471551 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000598.5(IGFBP3):c.404-17C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,585,384 control chromosomes in the GnomAD database, including 32,915 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 ( 2966 hom., cov: 31)

Exomes 𝑓: 0.20 ( 29949 hom. )

Consequence

IGFBP3
NM_000598.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Variant links:

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]

IGFBP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
IGFBP3	NM_000598.5 linkuse as main transcript	c.404-17C>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2 linkuse as main transcript	c.422-17C>G	splice_polypyrimidine_tract_variant, intron_variant		NP_001013416.1
IGFBP3	XM_047420325.1 linkuse as main transcript	c.404-17C>G	splice_polypyrimidine_tract_variant, intron_variant		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5 linkuse as main transcript	c.404-17C>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000598.5	ENSP00000477772	P4	P17936-1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29251

AN:

151860

Hom.:

2958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.0333

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.193

AC:

44874

AN:

232984

Hom.:

4929

AF XY:

0.201

AC XY:

25245

AN XY:

125338

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.0342

Gnomad SAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.197

AC:

282928

AN:

1433406

Hom.:

29949

Cov.:

AF XY:

0.201

AC XY:

143329

AN XY:

711412

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.0248

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.208

GnomAD4 genome

AF:

0.193

AC:

29289

AN:

151978

Hom.:

2966

Cov.:

AF XY:

0.190

AC XY:

14072

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.0333

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.205

Hom.:

638

Bravo

AF:

0.194

Asia WGS

AF:

0.210

AC:

730

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.1

DANN

Benign

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over