8-9007935-CTTTTTTTTTTTTT-C

Variant summary

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

The NM_153332.4(ERI1):c.109-18_109-6del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 969,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: ERI1 NM_153332.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

Genes affected

ERI1 (HGNC:23994): (exoribonuclease 1) Enables 3'-5' exonuclease activity. Predicted to be involved in exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-9007935-CTTTTTTTTTTTTT-C is Benign according to our data. Variant chr8-9007935-CTTTTTTTTTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3042758.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERI1	NM_153332.4	c.109-18_109-6del		intron_variant		ENST00000250263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERI1	ENST00000250263.8	c.109-18_109-6del		intron_variant		1	NM_153332.4	P1
ERI1	ENST00000519292.5	c.109-18_109-6del		intron_variant		2		P1
ERI1	ENST00000520684.5	c.109-18_109-6del		intron_variant, NMD_transcript_variant		5
ERI1	ENST00000521844.1	c.*197-18_*197-6del		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.000857 AC: 56 AN: 65324 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00542

Gnomad SAS AF: 0.000867

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000277

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000249 AC: 225 AN: 903856 Hom.: 0 AF XY: 0.000236 AC XY: 107 AN XY: 452590

Gnomad4 AFR exome AF: 0.00568

Gnomad4 AMR exome AF: 0.000523

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00153

Gnomad4 SAS exome AF: 0.0000708

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000794

Gnomad4 OTH exome AF: 0.000629

GnomAD4 genome AF: 0.000857 AC: 56 AN: 65340 Hom.: 0 Cov.: 0 AF XY: 0.000965 AC XY: 28 AN XY: 29024

Gnomad4 AFR AF: 0.00254

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00544

Gnomad4 SAS AF: 0.000865

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000277

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ERI1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 14, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs556702690; hg19: chr8-8865445;