10-49830251-G-C

Variant names:

• chr10-49830251-G-C
• rs7067802
• NM_003631.5:c.2647+2552C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_003631.5(PARG):​c.2647+2552C>G variant causes a intron change. The variant allele was found at a frequency of 0.19 in 152,182 control chromosomes in the GnomAD database, including 3,296 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 0.19 (3296 hom., cov: 33)
• Consequence: PARG NM_003631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

Genes affected

PARG (HGNC:8605): (poly(ADP-ribose) glycohydrolase) Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal proteins. The protein is found in many tissues and may be subject to proteolysis generating smaller, active products. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARG	NM_003631.5	c.2647+2552C>G		intron_variant	Intron 16 of 17	ENST00000616448.2	NP_003622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARG	ENST00000616448.2	c.2647+2552C>G		intron_variant	Intron 16 of 17	1	NM_003631.5	ENSP00000484285.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28953 AN: 152064 Hom.: 3296 Cov.: 33

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.190 AC: 28954 AN: 152182 Hom.: 3296 Cov.: 33 AF XY: 0.187 AC XY: 13944 AN XY: 74392

African (AFR) AF: 0.0756 AC: 3142 AN: 41548

American (AMR) AF: 0.167 AC: 2553 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3472

East Asian (EAS) AF: 0.0436 AC: 226 AN: 5180

South Asian (SAS) AF: 0.157 AC: 759 AN: 4824

European-Finnish (FIN) AF: 0.228 AC: 2412 AN: 10594

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18259 AN: 67962

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.223 Hom.: 521

Bravo AF: 0.177

Asia WGS AF: 0.0830 AC: 288 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Benign	0.71
PhyloP100		3.8

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: rs7067802; hg19: chr10-51038297;