Genetic Variant PABPC4:c.1669-92T>C (chr1-39562508-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135653.2(PABPC4):c.1669-92T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 884,302 control chromosomes in the GnomAD database, including 19,826 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 0.17 ( 2756 hom., cov: 33)

Exomes 𝑓: 0.20 ( 17070 hom. )

Consequence

PABPC4
NM_001135653.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.621

Variant links:

Genes affected

PABPC4 (HGNC:8557): (poly(A) binding protein cytoplasmic 4) Poly(A)-binding proteins (PABPs) bind to the poly(A) tail present at the 3-prime ends of most eukaryotic mRNAs. PABPC4 or IPABP (inducible PABP) was isolated as an activation-induced T-cell mRNA encoding a protein. Activation of T cells increased PABPC4 mRNA levels in T cells approximately 5-fold. PABPC4 contains 4 RNA-binding domains and proline-rich C terminus. PABPC4 is localized primarily to the cytoplasm. It is suggested that PABPC4 might be necessary for regulation of stability of labile mRNA species in activated T cells. PABPC4 was also identified as an antigen, APP1 (activated-platelet protein-1), expressed on thrombin-activated rabbit platelets. PABPC4 may also be involved in the regulation of protein translation in platelets and megakaryocytes or may participate in the binding or stabilization of polyadenylates in platelet dense granules. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. This protein has also been found to interact with coronavirus nucleocapsid proteins and is thought to inhibit coronavirus replication. [provided by RefSeq, Nov 2021]

PABPC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PABPC4	NM_001135653.2 link	c.1669-92T>C	intron_variant	Intron 12 of 15	ENST00000372858.8	NP_001129125.1	Q13310-3
PABPC4	NM_003819.4 link	c.1621-92T>C	intron_variant	Intron 12 of 15		NP_003810.1	Q13310-1
PABPC4	NM_001135654.2 link	c.1582-92T>C	intron_variant	Intron 11 of 14		NP_001129126.1	Q13310-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABPC4	ENST00000372858.8 link	c.1669-92T>C		intron_variant	Intron 12 of 15	1	NM_001135653.2	ENSP00000361949.3		Q13310-3

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25406

AN:

152134

Hom.:

2759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0435

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0766

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.203

AC:

148843

AN:

732050

Hom.:

17070

Cov.:

AF XY:

0.199

AC XY:

74554

AN XY:

375566

show subpopulations

Gnomad4 AFR exome

AF:

0.0389

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.0693

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.232

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.167

AC:

25400

AN:

152252

Hom.:

2756

Cov.:

AF XY:

0.164

AC XY:

12187

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0433

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0769

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.216

Hom.:

6320

Bravo

AF:

0.157

Asia WGS

AF:

0.0800

AC:

276

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.3

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over