5-50741547-C-T

Variant names:

• chr5-50741547-C-T
• rs282559
• NM_024615.4:c.147-8604C>T

Variant summary

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

The NM_024615.4(PARP8):​c.147-8604C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,246 control chromosomes in the GnomAD database, including 62,188 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 0.90 (62188 hom., cov: 33)
• Consequence: PARP8 NM_024615.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP8	NM_024615.4	c.147-8604C>T		intron_variant	Intron 2 of 25	ENST00000281631.10	NP_078891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP8	ENST00000281631.10	c.147-8604C>T		intron_variant	Intron 2 of 25	1	NM_024615.4	ENSP00000281631.4

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137427 AN: 152128 Hom.: 62131 Cov.: 33

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.903 AC: 137542 AN: 152246 Hom.: 62188 Cov.: 33 AF XY: 0.905 AC XY: 67387 AN XY: 74438

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.893

Alfa AF: 0.890 Hom.: 77577

Bravo AF: 0.901

Asia WGS AF: 0.921 AC: 3192 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.48

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: rs282559; hg19: chr5-50037381;