Genetic Variant IGF2BP1:c.402-1497T>C (chr17-49036671-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006546.4(IGF2BP1):c.402-1497T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,086 control chromosomes in the GnomAD database, including 26,370 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 ( 26363 hom., cov: 32)

Exomes 𝑓: 0.35 ( 7 hom. )

Consequence

IGF2BP1
NM_006546.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.928

Publications

6 publications found

Variant links:

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]

IGF2BP1 links:

RNU6-826P (HGNC:47789): (RNA, U6 small nuclear 826, pseudogene)

RNU6-826P links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 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.402-1497T>C		intron	N/A	NP_006537.3
	IGF2BP1	NM_001160423.2		c.401+4698T>C		intron	N/A	NP_001153895.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IGF2BP1	ENST00000290341.8	TSL:1 MANE Select	c.402-1497T>C	intron	N/A	ENSP00000290341.3
IGF2BP1	ENST00000431824.2	TSL:1	c.401+4698T>C	intron	N/A	ENSP00000389135.2
IGF2BP1	ENST00000925694.1		c.402-1497T>C	intron	N/A	ENSP00000595753.1

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86612

AN:

151906

Hom.:

26333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.780

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.527

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.516

GnomAD4 exome

AF:

0.355

AC:

AN:

Hom.:

Cov.:

AF XY:

0.283

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.400

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.570

AC:

86696

AN:

152024

Hom.:

26363

Cov.:

AF XY:

0.565

AC XY:

41960

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.780

AC:

32361

AN:

41494

American (AMR)

AF:

0.527

AC:

8042

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

1884

AN:

3470

East Asian (EAS)

AF:

0.216

AC:

1114

AN:

5168

South Asian (SAS)

AF:

0.444

AC:

2138

AN:

4816

European-Finnish (FIN)

AF:

0.480

AC:

5061

AN:

10542

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.507

AC:

34448

AN:

67948

Other (OTH)

AF:

0.511

AC:

1081

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1750

3499

5249

6998

8748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.519

Hom.:

26953

Bravo

AF:

0.581

Asia WGS

AF:

0.366

AC:

1274

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.5

(source)

DANN

Benign

0.36

PhyloP100

-0.93

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over