Variant chr7-23319261-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000258729.8(IGF2BP3):c.1204-7C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,582,884 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 10 hom., cov: 32)

Exomes 𝑓: 0.013 ( 156 hom. )

Consequence

IGF2BP3
ENST00000258729.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.003324

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.642

Variant links:

Genes affected

IGF2BP3 (HGNC:28868): (insulin like growth factor 2 mRNA binding protein 3) The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5' UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. A pseudogene exists on chromosome 7, and there are putative pseudogenes on other chromosomes. [provided by RefSeq, Jul 2008]

IGF2BP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-23319261-G-T is Benign according to our data. Variant chr7-23319261-G-T is described in ClinVar as [Benign]. Clinvar id is 774452.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0132 (18906/1430630) while in subpopulation NFE AF= 0.0154 (16748/1089392). AF 95% confidence interval is 0.0152. There are 156 homozygotes in gnomad4_exome. There are 9204 alleles in male gnomad4_exome subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP3	NM_006547.3 linkuse as main transcript	c.1204-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000258729.8	NP_006538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP3	ENST00000258729.8 linkuse as main transcript	c.1204-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006547.3	ENSP00000258729	P1	O00425-1

Frequencies

GnomAD3 genomes

AF:

0.00948

AC:

1442

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0127

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00931

AC:

2233

AN:

239824

Hom.:

AF XY:

0.00916

AC XY:

1187

AN XY:

129530

show subpopulations

Gnomad AFR exome

AF:

0.00307

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00737

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.00511

Gnomad FIN exome

AF:

0.00461

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0132

AC:

18906

AN:

1430630

Hom.:

156

Cov.:

AF XY:

0.0129

AC XY:

9204

AN XY:

712628

show subpopulations

Gnomad4 AFR exome

AF:

0.00271

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.00652

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.00513

Gnomad4 FIN exome

AF:

0.00444

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.00948

AC:

1443

AN:

152254

Hom.:

Cov.:

AF XY:

0.00910

AC XY:

677

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00330

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.0147

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0129

EpiControl

AF:

0.0125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0033

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: -44

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over