chr17-48998553-G-A

Variant names:

• chr17-48998553-G-A
• rs4794017
• NM_006546.4:c.176-556G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000250838 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006546.4. 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
	IGF2BP1	NM_006546.4	MANE Select	c.176-556G>A		intron	N/A	NP_006537.3
	IGF2BP1	NM_001160423.2		c.176-556G>A		intron	N/A	NP_001153895.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP1	ENST00000290341.8	TSL:1 MANE Select	c.176-556G>A		intron	N/A	ENSP00000290341.3
	IGF2BP1	ENST00000431824.2	TSL:1	c.176-556G>A		intron	N/A	ENSP00000389135.2
	IGF2BP1	ENST00000510023.5	TSL:3	n.436-556G>A		intron	N/A

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

African (AFR) AF: 0.740 AC: 30678 AN: 41464

American (AMR) AF: 0.493 AC: 7541 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3472

East Asian (EAS) AF: 0.647 AC: 3305 AN: 5112

South Asian (SAS) AF: 0.410 AC: 1971 AN: 4812

European-Finnish (FIN) AF: 0.272 AC: 2884 AN: 10588

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20760 AN: 67894

Other (OTH) AF: 0.445 AC: 940 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		0.057
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: rs4794017; hg19: chr17-47075915;