chr18-47156119-A-G

Variant names:

• chr18-47156119-A-G
• rs150586939
• NM_016097.5:c.*58T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 Likely benign (★).

• 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: Likely benign criteria provided, single submitter P:1 B:3
• Conservation: PhyloP100: 0.129
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly, epilepsy, and diabetes syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• primary microcephaly-epilepsy-permanent neonatal diabetes syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ENSG00000267228 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016097.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IER3IP1	NM_016097.5	MANE Select	c.*58T>C		3_prime_UTR	Exon 3 of 3	NP_057181.1	Q9Y5U9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IER3IP1	ENST00000256433.6	TSL:1 MANE Select	c.*58T>C		3_prime_UTR	Exon 3 of 3	ENSP00000256433.3	Q9Y5U9
	ENSG00000267228	ENST00000588705.1	TSL:2	n.*58T>C		splice_region non_coding_transcript_exon	Exon 3 of 6	ENSP00000465194.1
	ENSG00000267228	ENST00000588705.1	TSL:2	n.*58T>C		3_prime_UTR	Exon 3 of 6	ENSP00000465194.1

Frequencies

GnomAD3 genomes AF: 0.00524 AC: 798 AN: 152182 Hom.: 27 Cov.: 32

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.: 12 AF XY: 0.00455 AC XY: 2148 AN XY: 472322

African (AFR) AF: 0.00107 AC: 24 AN: 22440

American (AMR) AF: 0.000211 AC: 9 AN: 42572

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 78 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: 2 AN: 3860

European-Non Finnish (NFE) AF: 0.000596 AC: 362 AN: 607234

Other (OTH) AF: 0.00828 AC: 348 AN: 42044

GnomAD4 genome AF: 0.00524 AC: 798 AN: 152300 Hom.: 27 Cov.: 32 AF XY: 0.00593 AC XY: 442 AN XY: 74482

African (AFR) AF: 0.00123 AC: 51 AN: 41574

American (AMR) AF: 0.00216 AC: 33 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.109 AC: 564 AN: 5192

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4826

European-Finnish (FIN) AF: 0.00547 AC: 58 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68026

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00191 Hom.: 1

Bravo AF: 0.00603

Asia WGS AF: 0.0460 AC: 160 AN: 3474

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Epilepsy (1)
-	-	1	IER3IP1-related disorder (1)
-	-	1	not specified (1)
1	-	-	Self-limited epilepsy with centrotemporal spikes (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
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)

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

Other links and lift over

dbSNP: rs150586939; hg19: chr18-44682490; COSMIC: COSV107209187; COSMIC: COSV107209187;