rs9341178

Variant names:

• chr2-216654217-A-G
• rs9341178
• NM_000597.3:c.443-6340A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000597.3(IGFBP2):​c.443-6340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,070 control chromosomes in the GnomAD database, including 1,590 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 0.093 (1590 hom., cov: 32)
• Consequence: IGFBP2 NM_000597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• Publications: 1 publications found

Genes affected

IGFBP2 (HGNC:5471): (insulin like growth factor binding protein 2) The protein encoded by this gene is one of six similar proteins that bind insulin-like growth factors I and II (IGF-I and IGF-II). The encoded protein can be secreted into the bloodstream, where it binds IGF-I and IGF-II with high affinity, or it can remain intracellular, interacting with many different ligands. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the patient. Several transcript variants, one encoding a secreted isoform and the others encoding nonsecreted isoforms, have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP2	NM_000597.3	c.443-6340A>G		intron_variant	Intron 1 of 3	ENST00000233809.9	NP_000588.3
IGFBP2	NM_001313992.2	c.-56-6340A>G		intron_variant	Intron 1 of 3		NP_001300921.1
IGFBP2	NM_001313993.2	c.-56-6340A>G		intron_variant	Intron 1 of 3		NP_001300922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP2	ENST00000233809.9	c.443-6340A>G		intron_variant	Intron 1 of 3	1	NM_000597.3	ENSP00000233809.4
IGFBP2	ENST00000434997.1	c.-56-6340A>G		intron_variant	Intron 1 of 2	3		ENSP00000401698.1
IGFBP2	ENST00000490362.1	n.538-6340A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14101 AN: 151952 Hom.: 1574 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0752

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0931 AC: 14156 AN: 152070 Hom.: 1590 Cov.: 32 AF XY: 0.0904 AC XY: 6718 AN XY: 74350

African (AFR) AF: 0.272 AC: 11256 AN: 41400

American (AMR) AF: 0.0418 AC: 638 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00893 AC: 43 AN: 4816

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1428 AN: 68006

Other (OTH) AF: 0.0744 AC: 157 AN: 2110

Alfa AF: 0.0387 Hom.: 690

Bravo AF: 0.103

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.71
PhyloP100		-0.63
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: rs9341178; hg19: chr2-217518940;