Variant 8-9003110-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_153332.4(ERI1):c.47T>C(p.Leu16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 1,246,258 control chromosomes in the GnomAD database, including 501,155 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.87 ( 58218 hom., cov: 35)

Exomes 𝑓: 0.90 ( 442937 hom. )

Consequence

ERI1
NM_153332.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0340

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 (MetaRNN=7.8196734E-7).

BP6

Variant 8-9003110-T-C is Benign according to our data. Variant chr8-9003110-T-C is described in ClinVar as [Benign]. Clinvar id is 3060400.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERI1	NM_153332.4 linkuse as main transcript	c.47T>C	p.Leu16Pro	missense_variant	1/7	ENST00000250263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ERI1	ENST00000250263.8 linkuse as main transcript	c.47T>C	p.Leu16Pro	missense_variant	1/7	1	NM_153332.4	P1
ERI1	ENST00000519292.5 linkuse as main transcript	c.47T>C	p.Leu16Pro	missense_variant	1/8	2		P1
ERI1	ENST00000520684.5 linkuse as main transcript	c.47T>C	p.Leu16Pro	missense_variant, NMD_transcript_variant	1/6	5
ERI1	ENST00000521844.1 linkuse as main transcript	c.47T>C	p.Leu16Pro	missense_variant, NMD_transcript_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.873

AC:

132825

AN:

152168

Hom.:

58166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.813

Gnomad AMI

AF:

0.889

Gnomad AMR

AF:

0.889

Gnomad ASJ

AF:

0.895

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.880

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.870

GnomAD3 exomes

AF:

0.889

AC:

11220

AN:

12616

Hom.:

5005

AF XY:

0.890

AC XY:

5674

AN XY:

6378

show subpopulations

Gnomad AFR exome

AF:

0.787

Gnomad AMR exome

AF:

0.845

Gnomad ASJ exome

AF:

0.933

Gnomad EAS exome

AF:

0.725

Gnomad SAS exome

AF:

0.914

Gnomad FIN exome

AF:

0.889

Gnomad NFE exome

AF:

0.904

Gnomad OTH exome

AF:

0.911

GnomAD4 exome

AF:

0.899

AC:

984009

AN:

1093972

Hom.:

442937

Cov.:

AF XY:

0.900

AC XY:

465604

AN XY:

517396

show subpopulations

Gnomad4 AFR exome

AF:

0.811

Gnomad4 AMR exome

AF:

0.889

Gnomad4 ASJ exome

AF:

0.905

Gnomad4 EAS exome

AF:

0.774

Gnomad4 SAS exome

AF:

0.882

Gnomad4 FIN exome

AF:

0.890

Gnomad4 NFE exome

AF:

0.907

Gnomad4 OTH exome

AF:

0.885

GnomAD4 genome

AF:

0.873

AC:

132937

AN:

152286

Hom.:

58218

Cov.:

AF XY:

0.869

AC XY:

64748

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.814

Gnomad4 AMR

AF:

0.889

Gnomad4 ASJ

AF:

0.895

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.881

Gnomad4 FIN

AF:

0.889

Gnomad4 NFE

AF:

0.910

Gnomad4 OTH

AF:

0.870

Alfa

AF:

0.899

Hom.:

79177

Bravo

AF:

0.867

TwinsUK

AF:

0.904

AC:

3352

ALSPAC

AF:

0.902

AC:

3478

ESP6500AA

AF:

0.848

AC:

2615

ESP6500EA

AF:

0.924

AC:

5392

ExAC

AF:

0.767

AC:

10509

Asia WGS

AF:

0.809

AC:

2814

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ERI1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 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

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

Cadd

Benign

8.6

Dann

Benign

0.51

DEOGEN2

Benign

0.067

T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0012

MetaRNN

Benign

7.8e-7

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.20

N;N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.56

PROVEAN

Benign

1.4

N;N;N

REVEL

Benign

0.077

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.018

MPC

0.0063

ClinPred

0.0061

GERP RS

-0.96

Varity_R

0.081

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

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