Variant 1-241852289-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_130398.4(EXO1):c.162-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,601,104 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 166 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 166 hom. )

Consequence

EXO1
NM_130398.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001119

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.448

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:

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=-0.66).

BP6

Variant 1-241852289-T-C is Benign according to our data. Variant chr1-241852289-T-C is described in ClinVar as [Benign]. Clinvar id is 767770.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0874 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.162-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8 linkuse as main transcript	c.162-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_130398.4	ENSP00000355506	P2	Q9UQ84-1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3883

AN:

152196

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0896

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.00669

AC:

1674

AN:

250124

Hom.:

AF XY:

0.00474

AC XY:

642

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.0919

Gnomad AMR exome

AF:

0.00448

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00256

AC:

3705

AN:

1448790

Hom.:

166

Cov.:

AF XY:

0.00213

AC XY:

1537

AN XY:

721696

show subpopulations

Gnomad4 AFR exome

AF:

0.0909

Gnomad4 AMR exome

AF:

0.00486

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000454

Gnomad4 OTH exome

AF:

0.00637

GnomAD4 genome

AF:

0.0256

AC:

3904

AN:

152314

Hom.:

166

Cov.:

AF XY:

0.0251

AC XY:

1872

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0899

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0299

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EXO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 13, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.2

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.15

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