rs351974

Variant names:

• chr19-797079-A-C
• rs351974
• ENST00000635647.1:c.-419A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-797079-A-C
• chr19-797079-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635647.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP1	ENST00000635647.1	TSL:5	c.-419A>C		5_prime_UTR	Exon 1 of 14	ENSP00000489604.1	A0A0U1RRM4

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

African (AFR) AF: 0.602 AC: 673 AN: 1118

American (AMR) AF: 0.466 AC: 1075 AN: 2306

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 686 AN: 2268

East Asian (EAS) AF: 0.0719 AC: 143 AN: 1990

South Asian (SAS) AF: 0.421 AC: 9826 AN: 23324

European-Finnish (FIN) AF: 0.345 AC: 2248 AN: 6518

Middle Eastern (MID) AF: 0.283 AC: 107 AN: 378

European-Non Finnish (NFE) AF: 0.276 AC: 17129 AN: 62134

Other (OTH) AF: 0.331 AC: 1742 AN: 5266

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

African (AFR) AF: 0.614 AC: 25508 AN: 41532

American (AMR) AF: 0.457 AC: 6984 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3472

East Asian (EAS) AF: 0.0724 AC: 375 AN: 5176

South Asian (SAS) AF: 0.409 AC: 1975 AN: 4830

European-Finnish (FIN) AF: 0.346 AC: 3664 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19222 AN: 67988

Other (OTH) AF: 0.380 AC: 803 AN: 2114

Alfa AF: 0.312 Hom.: 13126

Bravo AF: 0.406

Asia WGS AF: 0.286 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		-0.64
PromoterAI		0.039	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs351974; hg19: chr19-797079;