18-47156242-GA-G

Position:

• chr18-47156242-GA-G

Variant summary

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

The NM_016097.5(IER3IP1):​c.194-11del 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 0.000767 in 1,388,954 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (0 hom.)
• 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-GA-G is Benign according to our data. Variant chr18-47156242-GA-G is described in ClinVar as [Benign]. Clinvar id is 1598829.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.194-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000256433.6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000279 AC: 4 AN: 143216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000201

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000308

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000853 AC: 1062 AN: 1245738 Hom.: 0 Cov.: 22 AF XY: 0.000819 AC XY: 510 AN XY: 622880

Gnomad4 AFR exome AF: 0.000955

Gnomad4 AMR exome AF: 0.00138

Gnomad4 ASJ exome AF: 0.000666

Gnomad4 EAS exome AF: 0.000225

Gnomad4 SAS exome AF: 0.000642

Gnomad4 FIN exome AF: 0.000429

Gnomad4 NFE exome AF: 0.000907

Gnomad4 OTH exome AF: 0.000658

GnomAD4 genome AF: 0.0000279 AC: 4 AN: 143216 Hom.: 0 Cov.: 32 AF XY: 0.0000288 AC XY: 2 AN XY: 69430

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000201

Gnomad4 SAS AF: 0.000220

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000308

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00233 Hom.: 0

Bravo AF: 0.0000227

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

Oct 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;