Genetic Variant PTBP1:c.9-71G>C (chr19-799342-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 publications found

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:

Genome browser will be placed here

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002819.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTBP1	NM_002819.5	MANE Select	c.9-71G>C	intron	N/A	NP_002810.1	P26599-3
PTBP1	NM_001411140.1		c.15-71G>C	intron	N/A	NP_001398069.1	A0A7I2V621
PTBP1	NM_031990.4		c.9-71G>C	intron	N/A	NP_114367.1	P26599-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTBP1	ENST00000356948.11	TSL:1 MANE Select	c.9-71G>C	intron	N/A	ENSP00000349428.4	P26599-3
PTBP1	ENST00000394601.8	TSL:1	c.9-71G>C	intron	N/A	ENSP00000408096.1	P26599-2
PTBP1	ENST00000349038.8	TSL:1	c.9-71G>C	intron	N/A	ENSP00000014112.5	P26599-1

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

GnomAD2 exomes

AF:

0.329

AC:

82449

AN:

250276

AF XY:

0.331

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 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

African (AFR)

AF:

0.339

AC:

10208

AN:

30120

American (AMR)

AF:

0.464

AC:

20636

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7422

AN:

25130

East Asian (EAS)

AF:

0.0640

AC:

2494

AN:

38954

South Asian (SAS)

AF:

0.422

AC:

35058

AN:

83060

European-Finnish (FIN)

AF:

0.365

AC:

19135

AN:

52496

Middle Eastern (MID)

AF:

0.331

AC:

1783

AN:

5390

European-Non Finnish (NFE)

AF:

0.290

AC:

280727

AN:

968102

Other (OTH)

AF:

0.311

AC:

17151

AN:

55078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

13112

26224

39335

52447

65559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8728

17456

26184

34912

43640

<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:

0.323

AC:

49122

AN:

152202

Hom.:

8346

Cov.:

AF XY:

0.330

AC XY:

24556

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.330

AC:

13720

AN:

41544

American (AMR)

AF:

0.431

AC:

6593

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1023

AN:

3472

East Asian (EAS)

AF:

0.0662

AC:

343

AN:

5184

South Asian (SAS)

AF:

0.412

AC:

1984

AN:

4820

European-Finnish (FIN)

AF:

0.364

AC:

3857

AN:

10584

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20705

AN:

67994

Other (OTH)

AF:

0.323

AC:

683

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1751

3502

5254

7005

8756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.249

Hom.:

886

Bravo

AF:

0.321

Asia WGS

AF:

0.270

AC:

940

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.52

PhyloP100

-0.22

PromoterAI

-0.0019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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