Genetic Variant EXO1:c.-303C>T (chr1-241848847-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006027.4(EXO1):c.-198C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,996 control chromosomes in the GnomAD database, including 16,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16617 hom., cov: 32)

Exomes 𝑓: 0.40 ( 1 hom. )

Consequence

EXO1
NM_006027.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.409

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

Lynch syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

EXO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006027.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EXO1	NM_130398.4	MANE Select	c.-303C>T	5_prime_UTR	Exon 2 of 16	NP_569082.2
EXO1	NM_006027.4		c.-198C>T	5_prime_UTR	Exon 1 of 14	NP_006018.4
EXO1	NM_001319224.2		c.-198C>T	5_prime_UTR	Exon 2 of 15	NP_001306153.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EXO1	ENST00000366548.8	TSL:1 MANE Select	c.-303C>T	5_prime_UTR	Exon 2 of 16	ENSP00000355506.3
EXO1	ENST00000348581.9	TSL:1	c.-198C>T	5_prime_UTR	Exon 1 of 14	ENSP00000311873.5
EXO1	ENST00000518483.5	TSL:1	c.-198C>T	5_prime_UTR	Exon 1 of 14	ENSP00000430251.1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70569

AN:

151868

Hom.:

16594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.400

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.465

AC:

70637

AN:

151986

Hom.:

16617

Cov.:

AF XY:

0.466

AC XY:

34643

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.471

AC:

19513

AN:

41440

American (AMR)

AF:

0.447

AC:

6832

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1273

AN:

3470

East Asian (EAS)

AF:

0.709

AC:

3660

AN:

5164

South Asian (SAS)

AF:

0.430

AC:

2073

AN:

4826

European-Finnish (FIN)

AF:

0.456

AC:

4809

AN:

10542

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.456

AC:

30998

AN:

67964

Other (OTH)

AF:

0.475

AC:

1001

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1931

3863

5794

7726

9657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.455

Hom.:

20505

Bravo

AF:

0.464

Asia WGS

AF:

0.552

AC:

1916

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.6

(source)

DANN

Benign

0.75

PhyloP100

-0.41

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over