Variant chr8-9007980-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153332.4(ERI1):c.119A>C(p.Gln40Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,152,380 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

ERI1
NM_153332.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.651

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035370827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERI1	NM_153332.4 linkuse as main transcript	c.119A>C	p.Gln40Pro	missense_variant	2/7	ENST00000250263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ERI1	ENST00000250263.8 linkuse as main transcript	c.119A>C	p.Gln40Pro	missense_variant	2/7	1	NM_153332.4	P1
ERI1	ENST00000519292.5 linkuse as main transcript	c.119A>C	p.Gln40Pro	missense_variant	2/8	2		P1
ERI1	ENST00000520684.5 linkuse as main transcript	c.119A>C	p.Gln40Pro	missense_variant, NMD_transcript_variant	2/6	5
ERI1	ENST00000521844.1 linkuse as main transcript	c.*207A>C		3_prime_UTR_variant, NMD_transcript_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000347

AC:

AN:

115436

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

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:

0.0000498

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000274

AC:

AN:

219102

Hom.:

AF XY:

0.0000336

AC XY:

AN XY:

119086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000578

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

128

AN:

1036944

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

519832

show subpopulations

Gnomad4 AFR exome

AF:

0.0000393

Gnomad4 AMR exome

AF:

0.0000324

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000157

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.0000347

AC:

AN:

115436

Hom.:

Cov.:

AF XY:

0.0000378

AC XY:

AN XY:

52894

show subpopulations

Gnomad4 AFR

AF:

0.0000326

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:

0.0000498

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000121

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.119A>C (p.Q40P) alteration is located in exon 2 (coding exon 2) of the ERI1 gene. This alteration results from a A to C substitution at nucleotide position 119, causing the glutamine (Q) at amino acid position 40 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.1

DANN

Benign

0.48

DEOGEN2

Benign

0.060

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.35

.;T;.

M_CAP

Benign

0.0062

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.23

N;N;N

REVEL

Benign

0.032

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.13

MVP

0.076

MPC

0.0069

ClinPred

0.011

GERP RS

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.082

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