7-4860464-A-G

Variant names:

• chr7-4860464-A-G
• rs1553960
• NM_020144.5:c.1347T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020144.5(PAPOLB):​c.1347T>C​(p.Asn449Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,613,522 control chromosomes in the GnomAD database, including 129,799 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 0.43 (14397 hom., cov: 33)
  • Exomes 𝑓: 0.39 (115402 hom.)
• Consequence: PAPOLB NM_020144.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 23 publications found

Genes affected

PAPOLB (HGNC:15970): (poly(A) polymerase beta) Predicted to enable polynucleotide adenylyltransferase activity. Predicted to be involved in mRNA polyadenylation. Predicted to be located in endoplasmic reticulum. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RADIL (HGNC:22226): (Rap associating with DIL domain) Predicted to enable GTPase binding activity. Acts upstream of or within substrate adhesion-dependent cell spreading. Located in microtubule. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=0.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPOLB	NM_020144.5	c.1347T>C	p.Asn449Asn	synonymous_variant	Exon 1 of 1	ENST00000404991.2	NP_064529.4
RADIL	NM_018059.5	c.535+17141T>C		intron_variant	Intron 2 of 14	ENST00000399583.4	NP_060529.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPOLB	ENST00000404991.2	c.1347T>C	p.Asn449Asn	synonymous_variant	Exon 1 of 1	6	NM_020144.5	ENSP00000384700.2
RADIL	ENST00000399583.4	c.535+17141T>C		intron_variant	Intron 2 of 14	5	NM_018059.5	ENSP00000382492.3
RADIL	ENST00000445392.5	n.535+17141T>C		intron_variant	Intron 2 of 14	5		ENSP00000413403.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64618 AN: 151978 Hom.: 14385 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.398

GnomAD2 exomes AF: 0.401 AC: 100282 AN: 250302 AF XY: 0.406

Gnomad AFR exome AF: 0.540

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.442

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.386

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.394 AC: 575549 AN: 1461426 Hom.: 115402 Cov.: 38 AF XY: 0.398 AC XY: 289043 AN XY: 727050

African (AFR) AF: 0.558 AC: 18677 AN: 33470

American (AMR) AF: 0.341 AC: 15239 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 10038 AN: 26134

East Asian (EAS) AF: 0.444 AC: 17637 AN: 39696

South Asian (SAS) AF: 0.515 AC: 44412 AN: 86246

European-Finnish (FIN) AF: 0.301 AC: 16058 AN: 53420

Middle Eastern (MID) AF: 0.450 AC: 2593 AN: 5762

European-Non Finnish (NFE) AF: 0.384 AC: 426437 AN: 1111594

Other (OTH) AF: 0.405 AC: 24458 AN: 60382

GnomAD4 genome AF: 0.425 AC: 64677 AN: 152096 Hom.: 14397 Cov.: 33 AF XY: 0.420 AC XY: 31233 AN XY: 74354

African (AFR) AF: 0.542 AC: 22462 AN: 41478

American (AMR) AF: 0.365 AC: 5582 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3468

East Asian (EAS) AF: 0.434 AC: 2246 AN: 5170

South Asian (SAS) AF: 0.514 AC: 2481 AN: 4824

European-Finnish (FIN) AF: 0.309 AC: 3273 AN: 10580

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25951 AN: 67968

Other (OTH) AF: 0.399 AC: 842 AN: 2110

Alfa AF: 0.396 Hom.: 52059

Bravo AF: 0.430

Asia WGS AF: 0.485 AC: 1689 AN: 3478

EpiCase AF: 0.378

EpiControl AF: 0.388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.3
DANN	Benign	0.79
PhyloP100		0.050
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: rs1553960; hg19: chr7-4900095; COSMIC: COSV68199931; COSMIC: COSV68199931;