Variant 8-9007961-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_153332.4(ERI1):c.109-9T>G variant causes a 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 intron

Scores

Splicing: ADA: 0.00006980

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.570

Variant links:

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]

ERI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERI1	NM_153332.4 linkuse as main transcript	c.109-9T>G		intron_variant		ENST00000250263.8	NP_699163.2	Q8IV48A0A024R355

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ERI1	ENST00000250263.8 linkuse as main transcript	c.109-9T>G	intron_variant	1	NM_153332.4	ENSP00000250263.7	Q8IV48
ERI1	ENST00000519292.5 linkuse as main transcript	c.109-9T>G	intron_variant	2		ENSP00000430190.1	Q8IV48
ERI1	ENST00000520684.5 linkuse as main transcript	n.109-9T>G	intron_variant	5		ENSP00000430651.1	E5RIV7
ERI1	ENST00000521844.1 linkuse as main transcript	n.*197-9T>G	intron_variant	4		ENSP00000429043.1	E5RJM3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

676

AN:

136316

Hom.:

Cov.:

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.:

AF XY:

0.00112

AC XY:

110

AN XY:

98422

show subpopulations

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.:

Cov.:

AF XY:

0.000545

AC XY:

351

AN XY:

643550

show subpopulations

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.:

Cov.:

AF XY:

0.00462

AC XY:

305

AN XY:

65962

show subpopulations

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.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 20, 2018

- -

ERI1-related disorder

Benign:1

Benign, no assertion criteria provided

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over