chr18-47156242-GAA-G

Variant names:

• chr18-47156242-GAA-G
• rs553378864
• NM_016097.5:c.194-12_194-11delTT

Variant summary

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

The NM_016097.5(IER3IP1):​c.194-12_194-11delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,251,822 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: IER3IP1 NM_016097.5 intron
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000267228 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IER3IP1	NM_016097.5	c.194-12_194-11delTT		intron_variant	Intron 2 of 2	ENST00000256433.6	NP_057181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IER3IP1	ENST00000256433.6	c.194-12_194-11delTT		intron_variant	Intron 2 of 2	1	NM_016097.5	ENSP00000256433.3
ENSG00000267228	ENST00000588705.1	n.194-12_194-11delTT		intron_variant	Intron 2 of 5	2		ENSP00000465194.1
ENSG00000267228	ENST00000602459.6	n.92-19795_92-19794delTT		intron_variant	Intron 1 of 6	5		ENSP00000473358.1
ENSG00000267228	ENST00000602926.5	n.92-19795_92-19794delTT		intron_variant	Intron 1 of 2	2		ENSP00000473502.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000559 AC: 7 AN: 1251822 Hom.: 0 AF XY: 0.00000319 AC XY: 2 AN XY: 625984

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000524

Gnomad4 OTH exome AF: 0.0000192

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs553378864; hg19: chr18-44682613;