8-9007961-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_153332.4(ERI1):c.109-9T>G 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 0.000641 in 1,298,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0050 (1 hom., cov: 27)
  • Exomes 𝑓: 0.00064 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERI1 NM_153332.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006980
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.570

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-9007961-T-G is Benign according to our data. Variant chr8-9007961-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 712692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000641 (832/1298882) while in subpopulation AFR AF= 0.0245 (648/26494). AF 95% confidence interval is 0.0229. There are 2 homozygotes in gnomad4_exome. There are 351 alleles in male gnomad4_exome subpopulation. Median coverage is 40. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERI1	NM_153332.4	c.109-9T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000250263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERI1	ENST00000250263.8	c.109-9T>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_153332.4	P1
ERI1	ENST00000519292.5	c.109-9T>G		splice_polypyrimidine_tract_variant, intron_variant		2		P1
ERI1	ENST00000520684.5	c.109-9T>G		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5
ERI1	ENST00000521844.1	c.*197-9T>G		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 676 AN: 136316 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00134

Gnomad ASJ AF: 0.00148

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000233

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000771

Gnomad OTH AF: 0.00435

GnomAD3 exomes AF: 0.00166 AC: 293 AN: 176654 Hom.: 1 AF XY: 0.00112 AC XY: 110 AN XY: 98422

Gnomad AFR exome AF: 0.0231

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.000324

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.000641 AC: 832 AN: 1298882 Hom.: 2 Cov.: 40 AF XY: 0.000545 AC XY: 351 AN XY: 643550

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.000989

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000722

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000443

Gnomad4 OTH exome AF: 0.00140

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00496 AC: 677 AN: 136364 Hom.: 1 Cov.: 27 AF XY: 0.00462 AC XY: 305 AN XY: 65962

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.00134

Gnomad4 ASJ AF: 0.00148

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000233

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000771

Gnomad4 OTH AF: 0.00431

Alfa AF: 0.00259 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 20, 2018

- -

ERI1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 2019

This variant is classified as 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.7
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000070
dbscSNV1_RF	Benign	0.072
SpliceAI score (max)		0.0		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: rs201166261; hg19: chr8-8865471;