17-49003069-G-T

Variant names:

• chr17-49003069-G-T
• rs1994969
• NM_006546.4:c.236+3900G>T

Variant summary

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

The NM_006546.4(IGF2BP1):​c.236+3900G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,978 control chromosomes in the GnomAD database, including 27,640 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 0.59 (27640 hom., cov: 31)
• Consequence: IGF2BP1 NM_006546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 14 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]

LOC124904020 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 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.236+3900G>T		intron	N/A	NP_006537.3
	IGF2BP1	NM_001160423.2		c.236+3900G>T		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.236+3900G>T		intron	N/A	ENSP00000290341.3
	IGF2BP1	ENST00000431824.2	TSL:1	c.236+3900G>T		intron	N/A	ENSP00000389135.2
	IGF2BP1	ENST00000925694.1		c.236+3900G>T		intron	N/A	ENSP00000595753.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89102 AN: 151860 Hom.: 27594 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.587 AC: 89208 AN: 151978 Hom.: 27640 Cov.: 31 AF XY: 0.580 AC XY: 43082 AN XY: 74278

African (AFR) AF: 0.775 AC: 32171 AN: 41496

American (AMR) AF: 0.541 AC: 8270 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1975 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1113 AN: 5186

South Asian (SAS) AF: 0.452 AC: 2179 AN: 4822

European-Finnish (FIN) AF: 0.491 AC: 5166 AN: 10518

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36574 AN: 67912

Other (OTH) AF: 0.540 AC: 1136 AN: 2102

Alfa AF: 0.554 Hom.: 38746

Bravo AF: 0.597

Asia WGS AF: 0.369 AC: 1287 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.3
DANN	Benign	0.34
PhyloP100		-0.0080
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: rs1994969; hg19: chr17-47080431;