18-47156520-C-T

Position:

• chr18-47156520-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016097.5(IER3IP1):​c.194-288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,856 control chromosomes in the GnomAD database, including 23,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (23717 hom., cov: 31)
• Consequence: IER3IP1 NM_016097.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.33

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 18-47156520-C-T is Benign according to our data. Variant chr18-47156520-C-T is described in ClinVar as [Benign]. Clinvar id is 668869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IER3IP1	NM_016097.5	c.194-288G>A		intron_variant		ENST00000256433.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IER3IP1	ENST00000256433.6	c.194-288G>A		intron_variant		1	NM_016097.5	P1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84549 AN: 151736 Hom.: 23690 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.549

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.557 AC: 84617 AN: 151856 Hom.: 23717 Cov.: 31 AF XY: 0.554 AC XY: 41058 AN XY: 74170

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.547

Alfa AF: 0.577 Hom.: 3174

Bravo AF: 0.548

Asia WGS AF: 0.387 AC: 1350 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2668760; hg19: chr18-44682891; COSMIC: COSV56507243; COSMIC: COSV56507243;