1-7961680-G-A

Position:

• chr1-7961680-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000493373.5(PARK7):​c.-23-1083G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 153,500 control chromosomes in the GnomAD database, including 4,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4050 hom., cov: 33)
  • Exomes 𝑓: 0.13 (15 hom.)
• Consequence: PARK7 ENST00000493373.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.53

Genes affected

PARK7 (HGNC:16369): (Parkinsonism associated deglycase) The product of this gene belongs to the peptidase C56 family of proteins. It acts as a positive regulator of androgen receptor-dependent transcription. It may also function as a redox-sensitive chaperone, as a sensor for oxidative stress, and it apparently protects neurons against oxidative stress and cell death. Defects in this gene are the cause of autosomal recessive early-onset Parkinson disease 7. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-7961680-G-A is Benign according to our data. Variant chr1-7961680-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 298111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARK7	NM_007262.5			upstream_gene_variant		ENST00000338639.10	NP_009193.2
PARK7	NM_001123377.2			upstream_gene_variant			NP_001116849.1
PARK7	XM_005263424.4			upstream_gene_variant			XP_005263481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10			upstream_gene_variant		1	NM_007262.5	ENSP00000340278	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32055 AN: 152098 Hom.: 4034 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0636

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.125 AC: 161 AN: 1286 Hom.: 15 Cov.: 0 AF XY: 0.125 AC XY: 120 AN XY: 962

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.0682

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.211 AC: 32105 AN: 152214 Hom.: 4050 Cov.: 33 AF XY: 0.210 AC XY: 15649 AN XY: 74416

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.181

Alfa AF: 0.108 Hom.: 181

Bravo AF: 0.208

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Parkinson Disease, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.7
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17523802; hg19: chr1-8021740;