Variant chr18-47156119-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016097.5(IER3IP1):c.*58T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,055,584 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0052 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 186 hom. )

Consequence

IER3IP1
NM_016097.5 3_prime_UTR

Scores

Splicing: ADA: 0.00003319

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided P:1B:2

Conservation

PhyloP100: 0.129

Variant links:

Genes affected

IER3IP1 (HGNC:18550): (immediate early response 3 interacting protein 1) This gene encodes a small protein that is localized to the endoplasmic reticulum (ER) and may play a role in the ER stress response by mediating cell differentiation and apoptosis. Transcription of this gene is regulated by tumor necrosis factor alpha and specificity protein 1 (Sp1). Mutations in this gene may play a role in microcephaly, epilepsy, and diabetes syndrome (MEDS), and a pseudogene of this gene is located on the long arm of chromosome 12. [provided by RefSeq, Dec 2011]

IER3IP1 links:

ENSG00000267228 (HGNC:):

ENSG00000267228 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IER3IP1	NM_016097.5 link	c.*58T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000256433.6	NP_057181.1	Q9Y5U9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IER3IP1	ENST00000256433 link	c.*58T>C	3_prime_UTR_variant	Exon 3 of 3	1	NM_016097.5	ENSP00000256433.3	Q9Y5U9
ENSG00000267228	ENST00000588705.1 link	n.*58T>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 6	2		ENSP00000465194.1
ENSG00000267228	ENST00000588705.1 link	n.*58T>C	3_prime_UTR_variant	Exon 3 of 6	2		ENSP00000465194.1

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

798

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00717

GnomAD4 exome

AF:

0.00481

AC:

4347

AN:

903284

Hom.:

186

Cov.:

AF XY:

0.00455

AC XY:

2148

AN XY:

472322

show subpopulations

Gnomad4 AFR exome

AF:

0.00107

Gnomad4 AMR exome

AF:

0.000211

Gnomad4 ASJ exome

AF:

0.00346

Gnomad4 EAS exome

AF:

0.0850

Gnomad4 SAS exome

AF:

0.00172

Gnomad4 FIN exome

AF:

0.00473

Gnomad4 NFE exome

AF:

0.000596

Gnomad4 OTH exome

AF:

0.00828

GnomAD4 genome

AF:

0.00524

AC:

798

AN:

152300

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

442

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00547

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00191

Hom.:

Bravo

AF:

0.00603

Asia WGS

AF:

0.0460

AC:

160

AN:

3474

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Self-limited epilepsy with centrotemporal spikes

Pathogenic:1

Jan 01, 2017

Bioinformatics Core, Luxembourg Center for Systems Biomedicine

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: case-control

CAADphred>15 -

IER3IP1-related disorder

Benign:1

May 24, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Epilepsy

Benign:1

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: curation

NM_016097.4:c.*58T>C in the IER3IP1 gene has an allele frequency of 0.008 in the gnomAD database, including 12 homozygous occurrences. The allele frequency is 0.1321 in the Asian subpopulation (total allele is less than 2000). Benign computational verdict because benign prediction from DANN. Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS2; BP4. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.4

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

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