rs351974

chr19-797079-A-Cchr19-797079-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000635647.1(PTBP1):c.-419A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 257,494 control chromosomes in the GnomAD database, including 19,510 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 0.39 (13614 hom., cov: 34)
  • Exomes 𝑓: 0.32 (5896 hom.)
• Consequence: PTBP1 ENST00000635647.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTBP1	ENST00000635647.1	c.-419A>C		5_prime_UTR_variant	1/14	5

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59697 AN: 152074 Hom.: 13585 Cov.: 34

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0731

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.319 AC: 33629 AN: 105302 Hom.: 5896 Cov.: 0 AF XY: 0.332 AC XY: 19570 AN XY: 58934

Gnomad4 AFR exome AF: 0.602

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.0719

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.331

GnomAD4 genome AF: 0.393 AC: 59775 AN: 152192 Hom.: 13614 Cov.: 34 AF XY: 0.398 AC XY: 29614 AN XY: 74406

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.380

Alfa AF: 0.298 Hom.: 9207

Bravo AF: 0.406

Asia WGS AF: 0.286 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	1.6
Dann	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs351974; hg19: chr19-797079;