19-806673-T-C

Variant names:

• chr19-806673-T-C
• rs351976
• NM_002819.5:c.1119+117T>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.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
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002819.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP1	NM_002819.5	MANE Select	c.1119+117T>C		intron	N/A	NP_002810.1
	PTBP1	NM_001411140.1		c.1125+117T>C		intron	N/A	NP_001398069.1
	PTBP1	NM_031990.4		c.1098+117T>C		intron	N/A	NP_114367.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP1	ENST00000356948.11	TSL:1 MANE Select	c.1119+117T>C		intron	N/A	ENSP00000349428.4
	PTBP1	ENST00000394601.8	TSL:1	c.1098+117T>C		intron	N/A	ENSP00000408096.1
	PTBP1	ENST00000349038.8	TSL:1	c.1041+117T>C		intron	N/A	ENSP00000014112.5

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

African (AFR) AF: 0.770 AC: 13023 AN: 16912

American (AMR) AF: 0.484 AC: 4695 AN: 9710

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 4287 AN: 14440

East Asian (EAS) AF: 0.0675 AC: 1713 AN: 25370

South Asian (SAS) AF: 0.428 AC: 17938 AN: 41882

European-Finnish (FIN) AF: 0.363 AC: 14791 AN: 40742

Middle Eastern (MID) AF: 0.359 AC: 1303 AN: 3630

European-Non Finnish (NFE) AF: 0.291 AC: 194029 AN: 665684

Other (OTH) AF: 0.339 AC: 12816 AN: 37756

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

African (AFR) AF: 0.739 AC: 30672 AN: 41520

American (AMR) AF: 0.477 AC: 7287 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3466

East Asian (EAS) AF: 0.0666 AC: 345 AN: 5182

South Asian (SAS) AF: 0.423 AC: 2038 AN: 4822

European-Finnish (FIN) AF: 0.363 AC: 3848 AN: 10600

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20794 AN: 67956

Other (OTH) AF: 0.416 AC: 880 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.30
DANN	Benign	0.36
PhyloP100		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs351976; hg19: chr19-806673;