chr1-39562508-A-G

Variant names:

• chr1-39562508-A-G
• rs4660293
• NM_001135653.2:c.1669-92T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 129 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135653.2. 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
	PABPC4	NM_001135653.2	MANE Select	c.1669-92T>C		intron	N/A	NP_001129125.1	Q13310-3
	PABPC4	NM_003819.4		c.1621-92T>C		intron	N/A	NP_003810.1	Q13310-1
	PABPC4	NM_001135654.2		c.1582-92T>C		intron	N/A	NP_001129126.1	Q13310-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABPC4	ENST00000372858.8	TSL:1 MANE Select	c.1669-92T>C		intron	N/A	ENSP00000361949.3	Q13310-3
	PABPC4	ENST00000372857.7	TSL:1	c.1621-92T>C		intron	N/A	ENSP00000361948.3	Q13310-1
	PABPC4	ENST00000372856.7	TSL:1	c.1582-92T>C		intron	N/A	ENSP00000361947.3	Q13310-2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25406 AN: 152134 Hom.: 2759 Cov.: 33

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.: 10 AF XY: 0.199 AC XY: 74554 AN XY: 375566

African (AFR) AF: 0.0389 AC: 738 AN: 18956

American (AMR) AF: 0.124 AC: 3285 AN: 26592

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 3930 AN: 16792

East Asian (EAS) AF: 0.139 AC: 4730 AN: 34150

South Asian (SAS) AF: 0.0693 AC: 3957 AN: 57110

European-Finnish (FIN) AF: 0.225 AC: 10540 AN: 46934

Middle Eastern (MID) AF: 0.164 AC: 681 AN: 4142

European-Non Finnish (NFE) AF: 0.232 AC: 114215 AN: 491890

Other (OTH) AF: 0.191 AC: 6767 AN: 35484

GnomAD4 genome AF: 0.167 AC: 25400 AN: 152252 Hom.: 2756 Cov.: 33 AF XY: 0.164 AC XY: 12187 AN XY: 74432

African (AFR) AF: 0.0433 AC: 1801 AN: 41570

American (AMR) AF: 0.152 AC: 2328 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3470

East Asian (EAS) AF: 0.119 AC: 616 AN: 5186

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2462 AN: 10596

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16471 AN: 67994

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.210 Hom.: 13444

Bravo AF: 0.157

Asia WGS AF: 0.0800 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.3
DANN	Benign	0.85
PhyloP100		-0.62
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4660293; hg19: chr1-40028180; COSMIC: COSV107456019; COSMIC: COSV107456019;