19-799342-G-C

Variant names:

• chr19-799342-G-C
• rs8100561
• NM_002819.5:c.9-71G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002819.5(PTBP1):​c.9-71G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,455,048 control chromosomes in the GnomAD database, including 71,162 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 0.32 (8346 hom., cov: 34)
  • Exomes 𝑓: 0.30 (62816 hom.)
• Consequence: PTBP1 NM_002819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP1	NM_002819.5	c.9-71G>C		intron_variant	Intron 1 of 14	ENST00000356948.11	NP_002810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11	c.9-71G>C		intron_variant	Intron 1 of 14	1	NM_002819.5	ENSP00000349428.4

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49059 AN: 152084 Hom.: 8324 Cov.: 34

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.329 AC: 82449 AN: 250276 AF XY: 0.331

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.465

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.0579

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.303 AC: 394614 AN: 1302846 Hom.: 62816 Cov.: 20 AF XY: 0.307 AC XY: 201459 AN XY: 656558

African (AFR) AF: 0.339 AC: 10208 AN: 30120

American (AMR) AF: 0.464 AC: 20636 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 7422 AN: 25130

East Asian (EAS) AF: 0.0640 AC: 2494 AN: 38954

South Asian (SAS) AF: 0.422 AC: 35058 AN: 83060

European-Finnish (FIN) AF: 0.365 AC: 19135 AN: 52496

Middle Eastern (MID) AF: 0.331 AC: 1783 AN: 5390

European-Non Finnish (NFE) AF: 0.290 AC: 280727 AN: 968102

Other (OTH) AF: 0.311 AC: 17151 AN: 55078

GnomAD4 genome AF: 0.323 AC: 49122 AN: 152202 Hom.: 8346 Cov.: 34 AF XY: 0.330 AC XY: 24556 AN XY: 74404

African (AFR) AF: 0.330 AC: 13720 AN: 41544

American (AMR) AF: 0.431 AC: 6593 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3472

East Asian (EAS) AF: 0.0662 AC: 343 AN: 5184

South Asian (SAS) AF: 0.412 AC: 1984 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3857 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20705 AN: 67994

Other (OTH) AF: 0.323 AC: 683 AN: 2112

Alfa AF: 0.249 Hom.: 886

Bravo AF: 0.321

Asia WGS AF: 0.270 AC: 940 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	1.6
DANN	Benign	0.52
PhyloP100		-0.22
PromoterAI		-0.0019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8100561; hg19: chr19-799342; COSMIC: COSV62460259; COSMIC: COSV62460259;