rs7305141

Variant summary

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

The NM_002583.4(PAWR):​c.517-586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,140 control chromosomes in the GnomAD database, including 56,995 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 0.86 ( 56995 hom., cov: 32)

Consequence

PAWR
NM_002583.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0500

Publications

5 publications found
Variant links:
Genes affected
PAWR (HGNC:8614): (pro-apoptotic WT1 regulator) This gene encodes a tumor suppressor protein that selectively induces apoptosis in cancer cells through intracellular and extracellular mechanisms. The intracellular mechanism involves the inhibition of pro-survival pathways and the activation of Fas-mediated apoptosis, while the extracellular mechanism involves the binding of a secreted form of this protein to glucose regulated protein 78 (GRP78) on the cell surface, which leads to activation of the extrinsic apoptotic pathway. This gene is located on the unstable human chromosomal 12q21 region and is often deleted or mutated different tumors. The encoded protein also plays an important role in the progression of age-related diseases. [provided by RefSeq, Aug 2017]

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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=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002583.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PAWR
NM_002583.4
MANE Select
c.517-586C>T
intron
N/ANP_002574.2
PAWR
NM_001354732.2
c.517-586C>T
intron
N/ANP_001341661.1
PAWR
NM_001354733.2
c.517-586C>T
intron
N/ANP_001341662.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PAWR
ENST00000328827.9
TSL:1 MANE Select
c.517-586C>T
intron
N/AENSP00000328088.4
PAWR
ENST00000551712.1
TSL:3
c.352-586C>T
intron
N/AENSP00000448317.1
PAWR
ENST00000549050.1
TSL:5
n.57+10313C>T
intron
N/A

Frequencies

GnomAD3 genomes
AF:
0.862
AC:
131023
AN:
152022
Hom.:
56948
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.968
Gnomad AMI
AF:
0.840
Gnomad AMR
AF:
0.855
Gnomad ASJ
AF:
0.746
Gnomad EAS
AF:
0.715
Gnomad SAS
AF:
0.674
Gnomad FIN
AF:
0.834
Gnomad MID
AF:
0.638
Gnomad NFE
AF:
0.835
Gnomad OTH
AF:
0.842
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.862
AC:
131127
AN:
152140
Hom.:
56995
Cov.:
32
AF XY:
0.857
AC XY:
63745
AN XY:
74388
show subpopulations
African (AFR)
AF:
0.968
AC:
40219
AN:
41558
American (AMR)
AF:
0.855
AC:
13060
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.746
AC:
2590
AN:
3470
East Asian (EAS)
AF:
0.715
AC:
3690
AN:
5162
South Asian (SAS)
AF:
0.673
AC:
3244
AN:
4818
European-Finnish (FIN)
AF:
0.834
AC:
8799
AN:
10548
Middle Eastern (MID)
AF:
0.641
AC:
186
AN:
290
European-Non Finnish (NFE)
AF:
0.835
AC:
56802
AN:
67992
Other (OTH)
AF:
0.838
AC:
1771
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
906
1811
2717
3622
4528
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
886
1772
2658
3544
4430
<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:
0.831
Hom.:
55565
Bravo
AF:
0.869
Asia WGS
AF:
0.683
AC:
2370
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
4.1
DANN
Benign
0.48
PhyloP100
-0.050
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: rs7305141; hg19: chr12-80015573; COSMIC: COSV108124047; API