19-807442-G-C

Variant names:

• chr19-807442-G-C
• rs123698
• NM_002819.5:c.1120-427G>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.1120-427G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 167,156 control chromosomes in the GnomAD database, including 44,155 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 0.72 (40965 hom., cov: 32)
  • Exomes 𝑓: 0.63 (3190 hom.)
• Consequence: PTBP1 NM_002819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 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.1120-427G>C		intron	N/A	NP_002810.1
	PTBP1	NM_001411140.1		c.1126-427G>C		intron	N/A	NP_001398069.1
	PTBP1	NM_031990.4		c.1099-427G>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.1120-427G>C		intron	N/A	ENSP00000349428.4
	PTBP1	ENST00000394601.8	TSL:1	c.1099-427G>C		intron	N/A	ENSP00000408096.1
	PTBP1	ENST00000349038.8	TSL:1	c.1042-427G>C		intron	N/A	ENSP00000014112.5

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109674 AN: 152012 Hom.: 40913 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.634 AC: 9523 AN: 15026 Hom.: 3190 Cov.: 0 AF XY: 0.640 AC XY: 4979 AN XY: 7780

African (AFR) AF: 0.916 AC: 293 AN: 320

American (AMR) AF: 0.739 AC: 325 AN: 440

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 221 AN: 404

East Asian (EAS) AF: 0.583 AC: 323 AN: 554

South Asian (SAS) AF: 0.695 AC: 927 AN: 1334

European-Finnish (FIN) AF: 0.680 AC: 446 AN: 656

Middle Eastern (MID) AF: 0.611 AC: 44 AN: 72

European-Non Finnish (NFE) AF: 0.615 AC: 6404 AN: 10420

Other (OTH) AF: 0.654 AC: 540 AN: 826

GnomAD4 genome AF: 0.722 AC: 109789 AN: 152130 Hom.: 40965 Cov.: 32 AF XY: 0.725 AC XY: 53933 AN XY: 74376

African (AFR) AF: 0.925 AC: 38430 AN: 41550

American (AMR) AF: 0.728 AC: 11136 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1965 AN: 3470

East Asian (EAS) AF: 0.571 AC: 2952 AN: 5170

South Asian (SAS) AF: 0.702 AC: 3383 AN: 4822

European-Finnish (FIN) AF: 0.694 AC: 7337 AN: 10574

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42391 AN: 67936

Other (OTH) AF: 0.704 AC: 1488 AN: 2114

Alfa AF: 0.557 Hom.: 1564

Bravo AF: 0.728

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.77
DANN	Benign	0.69
PhyloP100		-0.17
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)		0.040		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: rs123698; hg19: chr19-807442;