chr19-797517-G-C

Variant summary

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

The NM_002819.5(PTBP1):​c.8+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,520,180 control chromosomes in the GnomAD database, including 17,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2200 hom., cov: 32)
Exomes 𝑓: 0.15 ( 15525 hom. )

Consequence

PTBP1
NM_002819.5 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -1.18
Variant links:
Genes affected
PTBP1 (HGNC:9583): (polypyrimidine tract binding protein 1) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA-binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has four repeats of quasi-RNA recognition motif (RRM) domains that bind RNAs. This protein binds to the intronic polypyrimidine tracts that requires pre-mRNA splicing and acts via the protein degradation ubiquitin-proteasome pathway. It may also promote the binding of U2 snRNP to pre-mRNAs. This protein is localized in the nucleoplasm and it is also detected in the perinucleolar structure. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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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=-0.72).
BP6
Variant 19-797517-G-C is Benign according to our data. Variant chr19-797517-G-C is described in ClinVar as [Benign]. Clinvar id is 1301493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTBP1NM_002819.5 linkc.8+12G>C intron_variant Intron 1 of 14 ENST00000356948.11 NP_002810.1 P26599-3
PTBP1NM_031990.4 linkc.8+12G>C intron_variant Intron 1 of 14 NP_114367.1 P26599-2
PTBP1NM_031991.4 linkc.8+12G>C intron_variant Intron 1 of 13 NP_114368.1 P26599-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTBP1ENST00000356948.11 linkc.8+12G>C intron_variant Intron 1 of 14 1 NM_002819.5 ENSP00000349428.4 P26599-3

Frequencies

GnomAD3 genomes
AF:
0.163
AC:
24656
AN:
151364
Hom.:
2188
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.196
Gnomad AMI
AF:
0.104
Gnomad AMR
AF:
0.206
Gnomad ASJ
AF:
0.186
Gnomad EAS
AF:
0.0493
Gnomad SAS
AF:
0.177
Gnomad FIN
AF:
0.101
Gnomad MID
AF:
0.240
Gnomad NFE
AF:
0.149
Gnomad OTH
AF:
0.178
GnomAD2 exomes
AF:
0.167
AC:
22265
AN:
133630
AF XY:
0.168
show subpopulations
Gnomad AFR exome
AF:
0.209
Gnomad AMR exome
AF:
0.204
Gnomad ASJ exome
AF:
0.191
Gnomad EAS exome
AF:
0.0459
Gnomad FIN exome
AF:
0.109
Gnomad NFE exome
AF:
0.162
Gnomad OTH exome
AF:
0.191
GnomAD4 exome
AF:
0.147
AC:
201211
AN:
1368710
Hom.:
15525
Cov.:
31
AF XY:
0.148
AC XY:
100471
AN XY:
677810
show subpopulations
Gnomad4 AFR exome
AF:
0.203
AC:
5760
AN:
28392
Gnomad4 AMR exome
AF:
0.201
AC:
6969
AN:
34710
Gnomad4 ASJ exome
AF:
0.190
AC:
4608
AN:
24198
Gnomad4 EAS exome
AF:
0.0387
AC:
1237
AN:
31944
Gnomad4 SAS exome
AF:
0.175
AC:
13621
AN:
77844
Gnomad4 FIN exome
AF:
0.105
AC:
4008
AN:
38066
Gnomad4 NFE exome
AF:
0.144
AC:
154964
AN:
1072572
Gnomad4 Remaining exome
AF:
0.159
AC:
8972
AN:
56594
Heterozygous variant carriers
0
7956
15912
23868
31824
39780
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
5724
11448
17172
22896
28620
<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:
0.163
AC:
24700
AN:
151470
Hom.:
2200
Cov.:
32
AF XY:
0.162
AC XY:
12024
AN XY:
74028
show subpopulations
Gnomad4 AFR
AF:
0.197
AC:
0.197091
AN:
0.197091
Gnomad4 AMR
AF:
0.206
AC:
0.205763
AN:
0.205763
Gnomad4 ASJ
AF:
0.186
AC:
0.186201
AN:
0.186201
Gnomad4 EAS
AF:
0.0487
AC:
0.048714
AN:
0.048714
Gnomad4 SAS
AF:
0.176
AC:
0.176214
AN:
0.176214
Gnomad4 FIN
AF:
0.101
AC:
0.100996
AN:
0.100996
Gnomad4 NFE
AF:
0.149
AC:
0.148891
AN:
0.148891
Gnomad4 OTH
AF:
0.175
AC:
0.175238
AN:
0.175238
Heterozygous variant carriers
0
1036
2071
3107
4142
5178
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
272
544
816
1088
1360
<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:
0.160
Hom.:
353
Bravo
AF:
0.171
Asia WGS
AF:
0.138
AC:
480
AN:
3452

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Oct 20, 2021
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
-0.72
CADD
Benign
2.2
DANN
Benign
0.73
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10414379; hg19: chr19-797517; COSMIC: COSV62458655; COSMIC: COSV62458655; API