rs166863

chr5-50741617-A-Gchr5-50741617-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024615.4(PARP8):c.147-8534A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,926 control chromosomes in the GnomAD database, including 23,557 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 0.54 (23557 hom., cov: 31)
• Consequence: PARP8 NM_024615.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.613

Genes affected

PARP8 (HGNC:26124): (poly(ADP-ribose) polymerase family member 8) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP8	NM_024615.4	c.147-8534A>G		intron_variant		ENST00000281631.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP8	ENST00000281631.10	c.147-8534A>G		intron_variant		1	NM_024615.4	P1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81282 AN: 151808 Hom.: 23550 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.561

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.535 AC: 81291 AN: 151926 Hom.: 23557 Cov.: 31 AF XY: 0.537 AC XY: 39913 AN XY: 74276

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.561

Alfa AF: 0.551 Hom.: 3442

Bravo AF: 0.521

Asia WGS AF: 0.510 AC: 1775 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.2
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs166863; hg19: chr5-50037451;