chr17-49007349-G-A

Position:

• chr17-49007349-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006546.4(IGF2BP1):​c.236+8180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,042 control chromosomes in the GnomAD database, including 26,270 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 0.57 (26270 hom., cov: 31)
• Consequence: IGF2BP1 NM_006546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP1	NM_006546.4	c.236+8180G>A		intron_variant		ENST00000290341.8	NP_006537.3
LOC124904020	XR_007065831.1	n.447-2543C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP1	ENST00000290341.8	c.236+8180G>A		intron_variant		1	NM_006546.4	ENSP00000290341	P1
IGF2BP1	ENST00000431824.2	c.236+8180G>A		intron_variant		1		ENSP00000389135
	ENST00000504865.3	n.357-2543C>T		intron_variant, non_coding_transcript_variant		5
IGF2BP1	ENST00000515586.5	n.219+8180G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86646 AN: 151924 Hom.: 26226 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.571 AC: 86751 AN: 152042 Hom.: 26270 Cov.: 31 AF XY: 0.563 AC XY: 41824 AN XY: 74308

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.526

Alfa AF: 0.503 Hom.: 30958

Bravo AF: 0.582

Asia WGS AF: 0.364 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.065
DANN	Benign	0.58

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: rs9674544; hg19: chr17-47084711;