7-45915374-G-C

Variant names:

• chr7-45915374-G-C
• rs35440925
• NM_000598.5:c.751-429C>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.751-429C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 175,574 control chromosomes in the GnomAD database, including 3,069 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 0.18 (2614 hom., cov: 33)
  • Exomes 𝑓: 0.19 (455 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000598.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	NM_000598.5	MANE Select	c.751-429C>G		intron	N/A	NP_000589.2
	IGFBP3	NM_001013398.2		c.769-429C>G		intron	N/A	NP_001013416.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.751-429C>G		intron	N/A	ENSP00000477772.2
	IGFBP3	ENST00000381083.9	TSL:5	c.769-429C>G		intron	N/A	ENSP00000370473.4
	IGFBP3	ENST00000381086.9	TSL:2	c.460-429C>G		intron	N/A	ENSP00000370476.4

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27518 AN: 152036 Hom.: 2609 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.187 AC: 4382 AN: 23420 Hom.: 455 Cov.: 0 AF XY: 0.194 AC XY: 2292 AN XY: 11814

African (AFR) AF: 0.175 AC: 100 AN: 572

American (AMR) AF: 0.160 AC: 194 AN: 1214

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 150 AN: 670

East Asian (EAS) AF: 0.0273 AC: 31 AN: 1134

South Asian (SAS) AF: 0.291 AC: 452 AN: 1554

European-Finnish (FIN) AF: 0.129 AC: 175 AN: 1352

Middle Eastern (MID) AF: 0.278 AC: 30 AN: 108

European-Non Finnish (NFE) AF: 0.192 AC: 2966 AN: 15410

Other (OTH) AF: 0.202 AC: 284 AN: 1406

GnomAD4 genome AF: 0.181 AC: 27551 AN: 152154 Hom.: 2614 Cov.: 33 AF XY: 0.178 AC XY: 13260 AN XY: 74390

African (AFR) AF: 0.169 AC: 6997 AN: 41490

American (AMR) AF: 0.172 AC: 2629 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3468

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5166

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4818

European-Finnish (FIN) AF: 0.126 AC: 1336 AN: 10598

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13531 AN: 68000

Other (OTH) AF: 0.218 AC: 460 AN: 2114

Alfa AF: 0.0870 Hom.: 104

Bravo AF: 0.180

Asia WGS AF: 0.193 AC: 674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.41
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35440925; hg19: chr7-45954973;