Genetic Variant ENST00000454429.2:n.296+415A>G (chr9-33799372-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000454429.2(UBE2R2-AS1):n.296+415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 577,094 control chromosomes in the GnomAD database, including 121,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.66 ( 29270 hom., cov: 33)

Exomes 𝑓: 0.66 ( 91774 hom. )

Consequence

UBE2R2-AS1
ENST00000454429.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.85

Publications

26 publications found

Variant links:

Genes affected

UBE2R2-AS1 (HGNC:49911): (UBE2R2 antisense RNA 1)

UBE2R2-AS1 links:

PRSS3 (HGNC:9486): (serine protease 3) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is expressed in the brain and pancreas and is resistant to common trypsin inhibitors. It is active on peptide linkages involving the carboxyl group of lysine or arginine. This gene is localized to the locus of T cell receptor beta variable orphans on chromosome 9. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2010]

PRSS3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 9-33799372-T-C is Benign according to our data. Variant chr9-33799372-T-C is described in CliVar as Benign. Clinvar id is 1246185.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS3	NM_002771.4 link	c.*192T>C		downstream_gene_variant		ENST00000379405.4	NP_002762.3	P35030-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS3	ENST00000379405.4 link	c.*192T>C		downstream_gene_variant		1	NM_002771.4	ENSP00000368715.3		P35030-3

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

94317

AN:

143682

Hom.:

29238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.650

Gnomad AMR

AF:

0.688

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.741

Gnomad SAS

AF:

0.711

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.578

Gnomad NFE

AF:

0.651

Gnomad OTH

AF:

0.657

GnomAD4 exome

AF:

0.665

AC:

287962

AN:

433292

Hom.:

91774

AF XY:

0.665

AC XY:

148804

AN XY:

223738

show subpopulations

African (AFR)

AF:

0.642

AC:

7573

AN:

11792

American (AMR)

AF:

0.685

AC:

11522

AN:

16816

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

7132

AN:

11566

East Asian (EAS)

AF:

0.773

AC:

23345

AN:

30186

South Asian (SAS)

AF:

0.722

AC:

22767

AN:

31550

European-Finnish (FIN)

AF:

0.677

AC:

25522

AN:

37702

Middle Eastern (MID)

AF:

0.651

AC:

1272

AN:

1954

European-Non Finnish (NFE)

AF:

0.646

AC:

173072

AN:

267808

Other (OTH)

AF:

0.659

AC:

15757

AN:

23918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

4936

9872

14809

19745

24681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1706

3412

5118

6824

8530

<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:

0.656

AC:

94403

AN:

143802

Hom.:

29270

Cov.:

AF XY:

0.660

AC XY:

46347

AN XY:

70270

show subpopulations

African (AFR)

AF:

0.640

AC:

24533

AN:

38318

American (AMR)

AF:

0.689

AC:

10105

AN:

14666

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

1946

AN:

3240

East Asian (EAS)

AF:

0.741

AC:

3801

AN:

5128

South Asian (SAS)

AF:

0.710

AC:

3344

AN:

4710

European-Finnish (FIN)

AF:

0.662

AC:

6651

AN:

10050

Middle Eastern (MID)

AF:

0.554

AC:

153

AN:

276

European-Non Finnish (NFE)

AF:

0.651

AC:

42018

AN:

64584

Other (OTH)

AF:

0.657

AC:

1292

AN:

1968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

1902

3804

5707

7609

9511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.615

Hom.:

96473

Asia WGS

AF:

0.693

AC:

2411

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 15, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.27

(source)

DANN

Benign

0.60

PhyloP100

-2.8

Mutation Taster

=61/39

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over