chr18-47156242-G-GA

Position:

• chr18-47156242-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_016097.5(IER3IP1):​c.194-11_194-10insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,230,330 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IER3IP1 NM_016097.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.679

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-47156242-G-GA is Benign according to our data. Variant chr18-47156242-G-GA is described in ClinVar as [Benign]. Clinvar id is 2897614.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IER3IP1	NM_016097.5	c.194-11_194-10insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000256433.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IER3IP1	ENST00000256433.6	c.194-11_194-10insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016097.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 143214 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.000112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000769

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00372 AC: 4575 AN: 1230330 Hom.: 0 Cov.: 22 AF XY: 0.00347 AC XY: 2137 AN XY: 615150

Gnomad4 AFR exome AF: 0.00399

Gnomad4 AMR exome AF: 0.00327

Gnomad4 ASJ exome AF: 0.00261

Gnomad4 EAS exome AF: 0.00129

Gnomad4 SAS exome AF: 0.00274

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.00405

Gnomad4 OTH exome AF: 0.00343

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000559 AC: 8 AN: 143214 Hom.: 0 Cov.: 32 AF XY: 0.0000432 AC XY: 3 AN XY: 69426

Gnomad4 AFR AF: 0.0000257

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000220

Gnomad4 FIN AF: 0.000112

Gnomad4 NFE AF: 0.0000769

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephaly, epilepsy, and diabetes syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 05, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs553378864; hg19: chr18-44682613;