dbSNP rs4149896: EXO1:c.543+20A>G (chr1-241857502-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_130398.4(EXO1):c.543+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 1,604,528 control chromosomes in the GnomAD database, including 7,703 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 0.078 ( 719 hom., cov: 32)

Exomes 𝑓: 0.086 ( 6984 hom. )

Consequence

EXO1
NM_130398.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.663

Publications

6 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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXO1	NM_130398.4 link	c.543+20A>G		intron_variant	Intron 7 of 15	ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8 link	c.543+20A>G		intron_variant	Intron 7 of 15	1	NM_130398.4	ENSP00000355506.3

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11835

AN:

152018

Hom.:

714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.0670

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.0537

Gnomad EAS

AF:

0.0842

Gnomad SAS

AF:

0.0947

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0819

Gnomad OTH

AF:

0.0844

GnomAD2 exomes

AF:

0.112

AC:

28041

AN:

251036

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.311

Gnomad ASJ exome

AF:

0.0474

Gnomad EAS exome

AF:

0.0752

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0824

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0860

AC:

124919

AN:

1452392

Hom.:

6984

Cov.:

AF XY:

0.0859

AC XY:

62078

AN XY:

723046

show subpopulations

African (AFR)

AF:

0.0150

AC:

500

AN:

33288

American (AMR)

AF:

0.296

AC:

13190

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

1267

AN:

26030

East Asian (EAS)

AF:

0.0970

AC:

3839

AN:

39570

South Asian (SAS)

AF:

0.0939

AC:

8073

AN:

85972

European-Finnish (FIN)

AF:

0.111

AC:

5902

AN:

53194

Middle Eastern (MID)

AF:

0.0555

AC:

285

AN:

5134

European-Non Finnish (NFE)

AF:

0.0790

AC:

87229

AN:

1104560

Other (OTH)

AF:

0.0772

AC:

4634

AN:

60012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

5178

10355

15533

20710

25888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3274

6548

9822

13096

16370

<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:

0.0778

AC:

11840

AN:

152136

Hom.:

719

Cov.:

AF XY:

0.0810

AC XY:

6023

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0206

AC:

854

AN:

41520

American (AMR)

AF:

0.194

AC:

2957

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0537

AC:

186

AN:

3466

East Asian (EAS)

AF:

0.0842

AC:

436

AN:

5180

South Asian (SAS)

AF:

0.0948

AC:

457

AN:

4820

European-Finnish (FIN)

AF:

0.107

AC:

1129

AN:

10572

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0819

AC:

5571

AN:

68000

Other (OTH)

AF:

0.0835

AC:

176

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

534

1067

1601

2134

2668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0798

Hom.:

117

Bravo

AF:

0.0833

Asia WGS

AF:

0.0920

AC:

323

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.089

(source)

DANN

Benign

0.40

PhyloP100

-0.66

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over