dbSNP rs115335961: TROAP-AS1:n.2812+163G>C (chr12-49295097-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The ENST00000553259.1(TROAP-AS1):n.2812+163G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,349,330 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 138 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 113 hom. )

Consequence

TROAP-AS1
ENST00000553259.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.18

Publications

1 publications found

Variant links:

Genes affected

TROAP-AS1 (HGNC:55453): (TROAP and PRPH antisense RNA 1)

TROAP-AS1 links:

PRPH (HGNC:9461): (peripherin) This gene encodes a cytoskeletal protein found in neurons of the peripheral nervous system. The encoded protein is a type III intermediate filament protein with homology to other cytoskeletal proteins such as desmin, and is a different protein that the peripherin found in photoreceptors. Mutations in this gene have been associated with susceptibility to amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]

PRPH Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
amyotrophic lateral sclerosis type 1
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

PRPH links:

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=-0.63).

BP6

Variant 12-49295097-C-G is Benign according to our data. Variant chr12-49295097-C-G is described in ClinVar as Benign. ClinVar VariationId is 1225705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000553259.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TROAP-AS1	NR_120449.1		n.2812+163G>C		intron	N/A
	PRPH	NM_006262.4	MANE Select	c.-104C>G		upstream_gene	N/A	NP_006253.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
TROAP-AS1	ENST00000553259.1	TSL:2	n.2812+163G>C	intron	N/A
TROAP-AS1	ENST00000797029.1		n.269-6734G>C	intron	N/A
TROAP-AS1	ENST00000797030.1		n.358-6734G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3507

AN:

152102

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0809

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0120

GnomAD4 exome

AF:

0.00244

AC:

2926

AN:

1197110

Hom.:

113

Cov.:

AF XY:

0.00206

AC XY:

1226

AN XY:

595526

show subpopulations

African (AFR)

AF:

0.0854

AC:

2383

AN:

27910

American (AMR)

AF:

0.00454

AC:

153

AN:

33676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22426

East Asian (EAS)

AF:

0.00

AC:

AN:

34652

South Asian (SAS)

AF:

0.000260

AC:

AN:

73032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35342

Middle Eastern (MID)

AF:

0.00299

AC:

AN:

5024

European-Non Finnish (NFE)

AF:

0.0000919

AC:

AN:

913872

Other (OTH)

AF:

0.00531

AC:

272

AN:

51176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

152

304

456

608

760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0231

AC:

3511

AN:

152220

Hom.:

138

Cov.:

AF XY:

0.0229

AC XY:

1703

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0808

AC:

3356

AN:

41540

American (AMR)

AF:

0.00804

AC:

123

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67982

Other (OTH)

AF:

0.0119

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0195

Hom.:

Bravo

AF:

0.0263

Asia WGS

AF:

0.00491

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

2.2

PromoterAI

0.035

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over