Variant 19-797517-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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]

PTBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein
PTBP1	NM_002819.5 linkuse as main transcript	c.8+12G>C	intron_variant	ENST00000356948.11	NP_002810.1
PTBP1	NM_031990.4 linkuse as main transcript	c.8+12G>C	intron_variant		NP_114367.1
PTBP1	NM_031991.4 linkuse as main transcript	c.8+12G>C	intron_variant		NP_114368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11 linkuse as main transcript	c.8+12G>C		intron_variant		1	NM_002819.5	ENSP00000349428	P2	P26599-3

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24656

AN:

151364

Hom.:

2188

Cov.:

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

GnomAD3 exomes

AF:

0.167

AC:

22265

AN:

133630

Hom.:

1874

AF XY:

0.168

AC XY:

12461

AN XY:

74318

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 SAS exome

AF:

0.180

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.:

AF XY:

0.148

AC XY:

100471

AN XY:

677810

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.0387

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

AF:

0.163

AC:

24700

AN:

151470

Hom.:

2200

Cov.:

AF XY:

0.162

AC XY:

12024

AN XY:

74028

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.0487

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.175

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 20, 2021	- -

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over