rs2471551

Variant names:

• chr7-45917456-G-C
• rs2471551
• NM_000598.5:c.404-17C>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.404-17C>G variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 33 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.404-17C>G		intron_variant	Intron 1 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.422-17C>G		intron_variant	Intron 1 of 4		NP_001013416.1
IGFBP3	XM_047420325.1	c.404-17C>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.404-17C>G		intron_variant	Intron 1 of 4	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29251 AN: 151860 Hom.: 2958 Cov.: 31

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

GnomAD2 exomes AF: 0.193 AC: 44874 AN: 232984 AF XY: 0.201

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 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.: 28 AF XY: 0.201 AC XY: 143329 AN XY: 711412

African (AFR) AF: 0.203 AC: 6664 AN: 32816

American (AMR) AF: 0.152 AC: 6523 AN: 42876

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6252 AN: 24488

East Asian (EAS) AF: 0.0248 AC: 979 AN: 39444

South Asian (SAS) AF: 0.320 AC: 26413 AN: 82638

European-Finnish (FIN) AF: 0.138 AC: 7252 AN: 52672

Middle Eastern (MID) AF: 0.332 AC: 1815 AN: 5468

European-Non Finnish (NFE) AF: 0.196 AC: 214686 AN: 1093698

Other (OTH) AF: 0.208 AC: 12344 AN: 59306

GnomAD4 genome AF: 0.193 AC: 29289 AN: 151978 Hom.: 2966 Cov.: 31 AF XY: 0.190 AC XY: 14072 AN XY: 74252

African (AFR) AF: 0.204 AC: 8461 AN: 41428

American (AMR) AF: 0.177 AC: 2704 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3472

East Asian (EAS) AF: 0.0333 AC: 172 AN: 5160

South Asian (SAS) AF: 0.294 AC: 1412 AN: 4800

European-Finnish (FIN) AF: 0.126 AC: 1326 AN: 10552

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

European-Non Finnish (NFE) AF: 0.200 AC: 13592 AN: 67974

Other (OTH) AF: 0.232 AC: 490 AN: 2112

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
PhyloP100		1.3
PromoterAI		-0.00040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2471551; hg19: chr7-45957055; COSMIC: COSV51872120; COSMIC: COSV51872120;