Genetic Variant PTBP1:c.1120-427G>C (chr19-807442-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002819.5(PTBP1):c.1120-427G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 167,156 control chromosomes in the GnomAD database, including 44,155 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 0.72 ( 40965 hom., cov: 32)

Exomes 𝑓: 0.63 ( 3190 hom. )

Consequence

PTBP1
NM_002819.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.172

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP1	NM_002819.5 link	c.1120-427G>C		intron_variant	Intron 10 of 14	ENST00000356948.11	NP_002810.1	P26599-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11 link	c.1120-427G>C		intron_variant	Intron 10 of 14	1	NM_002819.5	ENSP00000349428.4		P26599-3

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109674

AN:

152012

Hom.:

40913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.925

Gnomad AMI

AF:

0.559

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.566

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.701

Gnomad FIN

AF:

0.694

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.705

GnomAD4 exome

AF:

0.634

AC:

9523

AN:

15026

Hom.:

3190

Cov.:

AF XY:

0.640

AC XY:

4979

AN XY:

7780

show subpopulations

Gnomad4 AFR exome

AF:

0.916

Gnomad4 AMR exome

AF:

0.739

Gnomad4 ASJ exome

AF:

0.547

Gnomad4 EAS exome

AF:

0.583

Gnomad4 SAS exome

AF:

0.695

Gnomad4 FIN exome

AF:

0.680

Gnomad4 NFE exome

AF:

0.615

Gnomad4 OTH exome

AF:

0.654

GnomAD4 genome

AF:

0.722

AC:

109789

AN:

152130

Hom.:

40965

Cov.:

AF XY:

0.725

AC XY:

53933

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.925

Gnomad4 AMR

AF:

0.728

Gnomad4 ASJ

AF:

0.566

Gnomad4 EAS

AF:

0.571

Gnomad4 SAS

AF:

0.702

Gnomad4 FIN

AF:

0.694

Gnomad4 NFE

AF:

0.624

Gnomad4 OTH

AF:

0.704

Alfa

AF:

0.557

Hom.:

1564

Bravo

AF:

0.728

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.77

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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