rs2276201

Variant names:

• chr6-162728465-T-C
• rs2276201
• NM_001080379.2:c.156+74T>C

Variant summary

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

The NM_001080379.2(PACRG):​c.156+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,551,346 control chromosomes in the GnomAD database, including 80,048 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 0.40 (15141 hom., cov: 31)
  • Exomes 𝑓: 0.29 (64907 hom.)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• Publications: 14 publications found

Genes affected

PACRG (HGNC:19152): (parkin coregulated) This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson's disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson's disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080379.2. 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
	PACRG	NM_001080379.2	MANE Select	c.156+74T>C		intron	N/A	NP_001073848.1	Q96M98-2
	PACRG	NM_152410.3		c.156+74T>C		intron	N/A	NP_689623.2	Q96M98-1
	PACRG	NM_001080378.2		c.156+74T>C		intron	N/A	NP_001073847.1	Q96M98-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACRG	ENST00000366888.7	TSL:1 MANE Select	c.156+74T>C		intron	N/A	ENSP00000355854.2	Q96M98-2
	PACRG	ENST00000366889.6	TSL:1	c.156+74T>C		intron	N/A	ENSP00000355855.2	Q96M98-2
	PACRG	ENST00000337019.7	TSL:2	c.156+74T>C		intron	N/A	ENSP00000337946.3	Q96M98-1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61390 AN: 151778 Hom.: 15122 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.294 AC: 411451 AN: 1399450 Hom.: 64907 AF XY: 0.293 AC XY: 203093 AN XY: 693576

African (AFR) AF: 0.710 AC: 23102 AN: 32532

American (AMR) AF: 0.476 AC: 20266 AN: 42534

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 7721 AN: 24176

East Asian (EAS) AF: 0.197 AC: 7726 AN: 39176

South Asian (SAS) AF: 0.301 AC: 24387 AN: 80994

European-Finnish (FIN) AF: 0.223 AC: 8642 AN: 38742

Middle Eastern (MID) AF: 0.348 AC: 1928 AN: 5546

European-Non Finnish (NFE) AF: 0.278 AC: 299019 AN: 1077354

Other (OTH) AF: 0.320 AC: 18660 AN: 58396

GnomAD4 genome AF: 0.405 AC: 61444 AN: 151896 Hom.: 15141 Cov.: 31 AF XY: 0.400 AC XY: 29670 AN XY: 74238

African (AFR) AF: 0.693 AC: 28654 AN: 41370

American (AMR) AF: 0.465 AC: 7094 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3464

East Asian (EAS) AF: 0.198 AC: 1019 AN: 5146

South Asian (SAS) AF: 0.292 AC: 1403 AN: 4812

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10584

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.276 AC: 18765 AN: 67942

Other (OTH) AF: 0.391 AC: 824 AN: 2110

Alfa AF: 0.322 Hom.: 33909

Bravo AF: 0.436

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.1
DANN	Benign	0.64
PhyloP100		-0.60
PromoterAI		-0.0054	Neutral
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: rs2276201; hg19: chr6-163149497; COSMIC: COSV58234229; COSMIC: COSV58234229;