Variant 17-48999106-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006546.4(IGF2BP1):c.176-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,547,638 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 13 hom., cov: 28)

Exomes 𝑓: 0.00089 ( 14 hom. )

Consequence

IGF2BP1
NM_006546.4 splice_region, intron

Scores

Splicing: ADA: 0.00009460

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0280

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:

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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=-0.67).

BP6

Variant 17-48999106-T-C is Benign according to our data. Variant chr17-48999106-T-C is described in ClinVar as [Benign]. Clinvar id is 789658.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00867 (1247/143800) while in subpopulation AFR AF= 0.0312 (1195/38242). AF 95% confidence interval is 0.0298. There are 13 homozygotes in gnomad4. There are 589 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP1	NM_006546.4 link	c.176-3T>C		splice_region_variant, intron_variant		ENST00000290341.8	NP_006537.3	Q9NZI8-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
IGF2BP1	ENST00000290341.8 link	c.176-3T>C	splice_region_variant, intron_variant	1	NM_006546.4	ENSP00000290341.3	Q9NZI8-1
IGF2BP1	ENST00000431824.2 link	c.176-3T>C	splice_region_variant, intron_variant	1		ENSP00000389135.2	Q9NZI8-2
IGF2BP1	ENST00000510023.5 link	n.436-3T>C	splice_region_variant, intron_variant	3
IGF2BP1	ENST00000515586.5 link	n.159-3T>C	splice_region_variant, intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00865

AC:

1243

AN:

143718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00234

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000215

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00388

Gnomad NFE

AF:

0.0000447

Gnomad OTH

AF:

0.00866

GnomAD3 exomes

AF:

0.00225

AC:

559

AN:

248288

Hom.:

AF XY:

0.00185

AC XY:

250

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.0305

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000801

Gnomad OTH exome

AF:

0.000996

GnomAD4 exome

AF:

0.000893

AC:

1254

AN:

1403838

Hom.:

Cov.:

AF XY:

0.000831

AC XY:

582

AN XY:

700764

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.00236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000588

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000263

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00867

AC:

1247

AN:

143800

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

589

AN XY:

69298

show subpopulations

Gnomad4 AFR

AF:

0.0312

Gnomad4 AMR

AF:

0.00233

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000216

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000448

Gnomad4 OTH

AF:

0.00860

Alfa

AF:

0.00420

Hom.:

Bravo

AF:

0.0100

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

Jul 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.9

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000095

dbscSNV1_RF

Benign

0.026

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

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