ENST00000588705.1:n.*58T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000588705.1(ENSG00000267228):n.*58T>C variant causes a splice region, non coding transcript exon 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 186 hom. )

Consequence

ENSG00000267228
ENST00000588705.1 splice_region, non_coding_transcript_exon

Scores

Splicing: ADA: 0.00003319

Clinical Significance

Likely benign criteria provided, single submitter P:1B:3

Conservation

PhyloP100: 0.129

Publications

2 publications found

Variant links:

Genes affected

ENSG00000267228 (HGNC:):

ENSG00000267228 links:

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 Gene-Disease associations (from GenCC):

microcephaly, epilepsy, and diabetes syndrome 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
primary microcephaly-epilepsy-permanent neonatal diabetes syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

IER3IP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

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

BP6

Variant 18-47156119-A-G is Benign according to our data. Variant chr18-47156119-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 433137.Status of the report is criteria_provided_single_submitter, 1 stars.

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
ENSG00000267228	ENST00000588705.1 link	n.*58T>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 6	2		ENSP00000465194.1
IER3IP1	ENST00000256433.6 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	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

African (AFR)

AF:

0.00107

AC:

AN:

22440

American (AMR)

AF:

0.000211

AC:

AN:

42572

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

22562

East Asian (EAS)

AF:

0.0850

AC:

3148

AN:

37056

South Asian (SAS)

AF:

0.00172

AC:

125

AN:

72486

European-Finnish (FIN)

AF:

0.00473

AC:

251

AN:

53030

Middle Eastern (MID)

AF:

0.000518

AC:

AN:

3860

European-Non Finnish (NFE)

AF:

0.000596

AC:

362

AN:

607234

Other (OTH)

AF:

0.00828

AC:

348

AN:

42044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

196

393

589

786

982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.00524

AC:

798

AN:

152300

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

442

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41574

American (AMR)

AF:

0.00216

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.109

AC:

564

AN:

5192

South Asian (SAS)

AF:

0.00497

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00547

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68026

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

121

162

202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00191

Hom.:

Bravo

AF:

0.00603

Asia WGS

AF:

0.0460

AC:

160

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, single submitter

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 -

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

DANN

Benign

0.64

PhyloP100

0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over