rs4794017

chr17-48998553-G-Achr17-48998553-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006546.4(IGF2BP1):c.176-556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,944 control chromosomes in the GnomAD database, including 18,720 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 0.46 (18720 hom., cov: 32)
• Consequence: IGF2BP1 NM_006546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

Genes affected

IGF2BP1 (HGNC:28866): (insulin like growth factor 2 mRNA binding protein 1) This gene encodes a member of the insulin-like growth factor 2 mRNA-binding protein family. The protein encoded by this gene contains four K homology domains and two RNA recognition motifs. It functions by binding to the mRNAs of certain genes, including insulin-like growth factor 2, beta-actin and beta-transducin repeat-containing protein, and regulating their translation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2BP1	NM_006546.4	c.176-556G>A		intron_variant		ENST00000290341.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2BP1	ENST00000290341.8	c.176-556G>A		intron_variant		1	NM_006546.4	P1
IGF2BP1	ENST00000431824.2	c.176-556G>A		intron_variant		1
IGF2BP1	ENST00000510023.5	n.436-556G>A		intron_variant, non_coding_transcript_variant		3
IGF2BP1	ENST00000515586.5	n.159-556G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69439 AN: 151828 Hom.: 18671 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.458 AC: 69551 AN: 151944 Hom.: 18720 Cov.: 32 AF XY: 0.457 AC XY: 33898 AN XY: 74254

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.445

Alfa AF: 0.363 Hom.: 1430

Bravo AF: 0.488

Asia WGS AF: 0.577 AC: 2004 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	15
Dann	Benign	0.97

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: rs4794017; hg19: chr17-47075915;