rs351995

Variant names:

• chr19-809732-C-A
• rs351995
• NM_002819.5:c.1464-811C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-809732-C-A
• chr19-809732-C-G

Variant summary

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

The NM_002819.5(PTBP1):​c.1464-811C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 151,892 control chromosomes in the GnomAD database, including 29,522 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 0.59 (29522 hom., cov: 31)
• Consequence: PTBP1 NM_002819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP1	NM_002819.5	c.1464-811C>A		intron_variant	Intron 13 of 14	ENST00000356948.11	NP_002810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11	c.1464-811C>A		intron_variant	Intron 13 of 14	1	NM_002819.5	ENSP00000349428.4

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90166 AN: 151774 Hom.: 29460 Cov.: 31

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.594 AC: 90291 AN: 151892 Hom.: 29522 Cov.: 31 AF XY: 0.599 AC XY: 44440 AN XY: 74234

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.556

Alfa AF: 0.544 Hom.: 2908

Bravo AF: 0.604

Asia WGS AF: 0.521 AC: 1811 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	0.64
DANN	Benign	0.39

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: rs351995; hg19: chr19-809732;