Variant 19-799342-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002819.5(PTBP1):c.9-71G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,455,048 control chromosomes in the GnomAD database, including 71,162 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 0.32 ( 8346 hom., cov: 34)

Exomes 𝑓: 0.30 ( 62816 hom. )

Consequence

PTBP1
NM_002819.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.217

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:

PTBP1 (HGNC:):

PTBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTBP1	NM_002819.5 linkuse as main transcript	c.9-71G>C		intron_variant		ENST00000356948.11	NP_002810.1	P26599-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11 linkuse as main transcript	c.9-71G>C		intron_variant		1	NM_002819.5	ENSP00000349428.4		P26599-3

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49059

AN:

152084

Hom.:

8324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.0668

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.329

AC:

82449

AN:

250276

Hom.:

14835

AF XY:

0.331

AC XY:

44887

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.465

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.0579

Gnomad SAS exome

AF:

0.427

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.303

AC:

394614

AN:

1302846

Hom.:

62816

Cov.:

AF XY:

0.307

AC XY:

201459

AN XY:

656558

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.464

Gnomad4 ASJ exome

AF:

0.295

Gnomad4 EAS exome

AF:

0.0640

Gnomad4 SAS exome

AF:

0.422

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.323

AC:

49122

AN:

152202

Hom.:

8346

Cov.:

AF XY:

0.330

AC XY:

24556

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.431

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.0662

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.249

Hom.:

886

Bravo

AF:

0.321

Asia WGS

AF:

0.270

AC:

940

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over