8-9007935-CTTTTTT-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_153332.4(ERI1):c.109-11_109-6del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 895,536 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.014 (1 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-9007935-CTTTTTT-C is Benign according to our data. Variant chr8-9007935-CTTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3037479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0138 (12355/895536) while in subpopulation EAS AF= 0.0181 (360/19930). AF 95% confidence interval is 0.0165. There are 1 homozygotes in gnomad4_exome. There are 6031 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERI1	NM_153332.4	c.109-11_109-6del		intron_variant		ENST00000250263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERI1	ENST00000250263.8	c.109-11_109-6del		intron_variant		1	NM_153332.4	P1
ERI1	ENST00000519292.5	c.109-11_109-6del		intron_variant		2		P1
ERI1	ENST00000520684.5	c.109-11_109-6del		intron_variant, NMD_transcript_variant		5
ERI1	ENST00000521844.1	c.*197-11_*197-6del		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 65322 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0000578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0138 AC: 12355 AN: 895536 Hom.: 1 AF XY: 0.0135 AC XY: 6031 AN XY: 448304

Gnomad4 AFR exome AF: 0.00823

Gnomad4 AMR exome AF: 0.00819

Gnomad4 ASJ exome AF: 0.0142

Gnomad4 EAS exome AF: 0.0181

Gnomad4 SAS exome AF: 0.00545

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000153 AC: 1 AN: 65322 Hom.: 0 Cov.: 0 AF XY: 0.0000345 AC XY: 1 AN XY: 29010

Gnomad4 AFR AF: 0.0000578

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

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

Mar 20, 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;