rs351976

Positions:

• chr19-806673-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002819.5(PTBP1):​c.1119+117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,008,274 control chromosomes in the GnomAD database, including 62,576 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 0.44 (17890 hom., cov: 34)
  • Exomes 𝑓: 0.31 (44686 hom.)
• Consequence: PTBP1 NM_002819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.03

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTBP1	NM_002819.5	c.1119+117T>C		intron_variant		ENST00000356948.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTBP1	ENST00000356948.11	c.1119+117T>C		intron_variant		1	NM_002819.5	P2

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67021 AN: 152028 Hom.: 17846 Cov.: 34

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.309 AC: 264595 AN: 856126 Hom.: 44686 Cov.: 11 AF XY: 0.312 AC XY: 131417 AN XY: 421574

Gnomad4 AFR exome AF: 0.770

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.0675

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.441 AC: 67117 AN: 152148 Hom.: 17890 Cov.: 34 AF XY: 0.445 AC XY: 33075 AN XY: 74398

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0666

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.416

Alfa AF: 0.395 Hom.: 1728

Bravo AF: 0.458

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.30
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs351976; hg19: chr19-806673;