rs11085226

Positions:

• chr19-799770-A-G

Variant summary

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

The NM_002819.5(PTBP1):​c.39+327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 152,228 control chromosomes in the GnomAD database, including 708 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 0.087 (708 hom., cov: 33)
• Consequence: PTBP1 NM_002819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTBP1	NM_002819.5	c.39+327A>G		intron_variant		ENST00000356948.11	NP_002810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11	c.39+327A>G		intron_variant		1	NM_002819.5	ENSP00000349428.4

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13278 AN: 152112 Hom.: 708 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0873 AC: 13283 AN: 152228 Hom.: 708 Cov.: 33 AF XY: 0.0880 AC XY: 6554 AN XY: 74442

Gnomad4 AFR AF: 0.0646

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0429

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0517

Gnomad4 NFE AF: 0.0904

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0966 Hom.: 1084

Bravo AF: 0.0949

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.52

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: rs11085226; hg19: chr19-799770;