NM_002819.5:c.8+12G>C

Variant names:

• chr19-797517-G-C
• rs10414379
• NM_002819.5:c.8+12G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002819.5(PTBP1):​c.8+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,520,180 control chromosomes in the GnomAD database, including 17,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2200 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15525 hom.)
• Consequence: PTBP1 NM_002819.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 19-797517-G-C is Benign according to our data. Variant chr19-797517-G-C is described in ClinVar as [Benign]. Clinvar id is 1301493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP1	NM_002819.5	c.8+12G>C		intron_variant	Intron 1 of 14	ENST00000356948.11	NP_002810.1
PTBP1	NM_031990.4	c.8+12G>C		intron_variant	Intron 1 of 14		NP_114367.1
PTBP1	NM_031991.4	c.8+12G>C		intron_variant	Intron 1 of 13		NP_114368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11	c.8+12G>C		intron_variant	Intron 1 of 14	1	NM_002819.5	ENSP00000349428.4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24656 AN: 151364 Hom.: 2188 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.167 AC: 22265 AN: 133630 AF XY: 0.168

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.0459

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.147 AC: 201211 AN: 1368710 Hom.: 15525 Cov.: 31 AF XY: 0.148 AC XY: 100471 AN XY: 677810

African (AFR) AF: 0.203 AC: 5760 AN: 28392

American (AMR) AF: 0.201 AC: 6969 AN: 34710

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4608 AN: 24198

East Asian (EAS) AF: 0.0387 AC: 1237 AN: 31944

South Asian (SAS) AF: 0.175 AC: 13621 AN: 77844

European-Finnish (FIN) AF: 0.105 AC: 4008 AN: 38066

Middle Eastern (MID) AF: 0.244 AC: 1072 AN: 4390

European-Non Finnish (NFE) AF: 0.144 AC: 154964 AN: 1072572

Other (OTH) AF: 0.159 AC: 8972 AN: 56594

GnomAD4 genome AF: 0.163 AC: 24700 AN: 151470 Hom.: 2200 Cov.: 32 AF XY: 0.162 AC XY: 12024 AN XY: 74028

African (AFR) AF: 0.197 AC: 8156 AN: 41382

American (AMR) AF: 0.206 AC: 3135 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3464

East Asian (EAS) AF: 0.0487 AC: 250 AN: 5132

South Asian (SAS) AF: 0.176 AC: 849 AN: 4818

European-Finnish (FIN) AF: 0.101 AC: 1055 AN: 10446

Middle Eastern (MID) AF: 0.238 AC: 69 AN: 290

European-Non Finnish (NFE) AF: 0.149 AC: 10079 AN: 67694

Other (OTH) AF: 0.175 AC: 368 AN: 2100

Alfa AF: 0.160 Hom.: 353

Bravo AF: 0.171

Asia WGS AF: 0.138 AC: 480 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.2
DANN	Benign	0.73
PhyloP100		-1.2
PromoterAI		-0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs10414379; hg19: chr19-797517; COSMIC: COSV62458655; COSMIC: COSV62458655;