Variant 1-241885372-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_130398.4(EXO1):c.2270C>T(p.Pro757Leu) variant causes a missense change. The variant allele was found at a frequency of 0.176 in 1,612,938 control chromosomes in the GnomAD database, including 27,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3100 hom., cov: 31)

Exomes 𝑓: 0.17 ( 24712 hom. )

Consequence

EXO1
NM_130398.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.47

Variant links:

Genes affected

EXO1 (HGNC:3511): (exonuclease 1) This gene encodes a protein with 5' to 3' exonuclease activity as well as an RNase H activity. It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in mismatch repair and recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms. [provided by RefSeq, Jul 2008]

EXO1 links:

EXO1 (HGNC:):

EXO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037188828).

BP6

Variant 1-241885372-C-T is Benign according to our data. Variant chr1-241885372-C-T is described in ClinVar as [Benign]. Clinvar id is 3060942.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXO1	NM_130398.4 linkuse as main transcript	c.2270C>T	p.Pro757Leu	missense_variant	15/16	ENST00000366548.8	NP_569082.2	Q9UQ84-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8 linkuse as main transcript	c.2270C>T	p.Pro757Leu	missense_variant	15/16	1	NM_130398.4	ENSP00000355506.3		Q9UQ84-1

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28757

AN:

151760

Hom.:

3099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.198

GnomAD3 exomes

AF:

0.210

AC:

52701

AN:

250846

Hom.:

6891

AF XY:

0.200

AC XY:

27105

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.429

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.174

AC:

254891

AN:

1461060

Hom.:

24712

Cov.:

AF XY:

0.173

AC XY:

125915

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.416

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.190

AC:

28794

AN:

151878

Hom.:

3100

Cov.:

AF XY:

0.193

AC XY:

14339

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.441

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.168

Hom.:

5855

Bravo

AF:

0.206

TwinsUK

AF:

0.163

AC:

604

ALSPAC

AF:

0.153

AC:

589

ESP6500AA

AF:

0.184

AC:

810

ESP6500EA

AF:

0.159

AC:

1367

ExAC

AF:

0.203

AC:

24657

Asia WGS

AF:

0.311

AC:

1083

AN:

3478

EpiCase

AF:

0.152

EpiControl

AF:

0.152

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EXO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 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

0.079

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;D;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

.;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

M;M;M

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.021

D;D;D

Sift4G

Uncertain

0.040

D;D;D

Polyphen

0.58

P;P;P

Vest4

0.13

MPC

0.19

ClinPred

0.047

GERP RS

6.0

Varity_R

0.12

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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