3-36988684-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014805.4(EPM2AIP1):​c.*2570G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,850 control chromosomes in the GnomAD database, including 21,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.52 ( 21380 hom., cov: 31)
Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

EPM2AIP1
NM_014805.4 3_prime_UTR

Scores

2

Clinical Significance

Benign reviewed by expert panel B:2

Conservation

PhyloP100: 0.120

Publications

24 publications found
Variant links:
Genes affected
EPM2AIP1 (HGNC:19735): (EPM2A interacting protein 1) The EPM2A gene, which encodes laforin, is mutated in an autosomal recessive form of adolescent progressive myoclonus epilepsy. The protein encoded by this gene binds to laforin, but its function is not known. This gene is intronless. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 3-36988684-C-A is Benign according to our data. Variant chr3-36988684-C-A is described in ClinVar as [Benign]. Clinvar id is 89594.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPM2AIP1NM_014805.4 linkc.*2570G>T 3_prime_UTR_variant Exon 1 of 1 ENST00000322716.8 NP_055620.1 Q7L775

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPM2AIP1ENST00000322716.8 linkc.*2570G>T 3_prime_UTR_variant Exon 1 of 1 6 NM_014805.4 ENSP00000406027.1 Q7L775
EPM2AIP1ENST00000623924.1 linkc.123-1455G>T intron_variant Intron 2 of 2 5 ENSP00000485489.1 A0A096LPB0

Frequencies

GnomAD3 genomes
AF:
0.516
AC:
78366
AN:
151726
Hom.:
21350
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.617
Gnomad AMI
AF:
0.582
Gnomad AMR
AF:
0.485
Gnomad ASJ
AF:
0.471
Gnomad EAS
AF:
0.0975
Gnomad SAS
AF:
0.268
Gnomad FIN
AF:
0.440
Gnomad MID
AF:
0.465
Gnomad NFE
AF:
0.526
Gnomad OTH
AF:
0.502
GnomAD4 exome
AF:
0.500
AC:
3
AN:
6
Hom.:
1
Cov.:
0
AF XY:
0.500
AC XY:
3
AN XY:
6
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.500
AC:
3
AN:
6
Other (OTH)
AC:
0
AN:
0
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.517
AC:
78453
AN:
151844
Hom.:
21380
Cov.:
31
AF XY:
0.507
AC XY:
37616
AN XY:
74186
show subpopulations
African (AFR)
AF:
0.617
AC:
25531
AN:
41368
American (AMR)
AF:
0.485
AC:
7412
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.471
AC:
1633
AN:
3468
East Asian (EAS)
AF:
0.0976
AC:
504
AN:
5166
South Asian (SAS)
AF:
0.268
AC:
1291
AN:
4822
European-Finnish (FIN)
AF:
0.440
AC:
4630
AN:
10516
Middle Eastern (MID)
AF:
0.452
AC:
131
AN:
290
European-Non Finnish (NFE)
AF:
0.526
AC:
35745
AN:
67928
Other (OTH)
AF:
0.497
AC:
1049
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1800
3601
5401
7202
9002
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
662
1324
1986
2648
3310
<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:
0.524
Hom.:
28406
Bravo
AF:
0.524
Asia WGS
AF:
0.237
AC:
828
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Lynch syndrome Benign:1
Sep 05, 2013
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Significance:Benign
Review Status:reviewed by expert panel
Collection Method:research

MAF >1% -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.7
DANN
Benign
0.59
PhyloP100
0.12
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs9311149; hg19: chr3-37030175; API