1-7962740-C-CT

Position:

• chr1-7962740-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007262.5(PARK7):​c.-23-4dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,138,026 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (32 hom., cov: 29)
  • Exomes 𝑓: 0.11 (4 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11

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 -10 ACMG points.

• BP6: Variant 1-7962740-C-CT is Benign according to our data. Variant chr1-7962740-C-CT is described in ClinVar as [Benign]. Clinvar id is 1182033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARK7	NM_007262.5	c.-23-4dup		intron_variant		ENST00000338639.10	NP_009193.2
PARK7	NM_001123377.2	c.-23-4dup		intron_variant			NP_001116849.1
PARK7	XM_005263424.4	c.-23-4dup		intron_variant			XP_005263481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10	c.-23-4dup		intron_variant		1	NM_007262.5	ENSP00000340278	P1

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 2318 AN: 115178 Hom.: 32 Cov.: 29

Gnomad AFR AF: 0.00886

Gnomad AMI AF: 0.00723

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00873

Gnomad EAS AF: 0.00419

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0199

GnomAD3 exomes AF: 0.0943 AC: 8487 AN: 89970 Hom.: 1 AF XY: 0.0925 AC XY: 4570 AN XY: 49406

Gnomad AFR exome AF: 0.0809

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0878

Gnomad EAS exome AF: 0.117

Gnomad SAS exome AF: 0.0897

Gnomad FIN exome AF: 0.0660

Gnomad NFE exome AF: 0.0945

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.106 AC: 108731 AN: 1022860 Hom.: 4 Cov.: 0 AF XY: 0.105 AC XY: 54290 AN XY: 517076

Gnomad4 AFR exome AF: 0.0692

Gnomad4 AMR exome AF: 0.0756

Gnomad4 ASJ exome AF: 0.0885

Gnomad4 EAS exome AF: 0.0856

Gnomad4 SAS exome AF: 0.0993

Gnomad4 FIN exome AF: 0.0768

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0201 AC: 2318 AN: 115166 Hom.: 32 Cov.: 29 AF XY: 0.0196 AC XY: 1080 AN XY: 55138

Gnomad4 AFR AF: 0.00885

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.00873

Gnomad4 EAS AF: 0.00420

Gnomad4 SAS AF: 0.0105

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.0317

Gnomad4 OTH AF: 0.0199

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs370370394; hg19: chr1-8022800;