rs6703670

Variant names:

• chr1-7970796-G-A
• rs6703670
• NM_007262.5:c.253-98G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007262.5(PARK7):​c.253-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,122,424 control chromosomes in the GnomAD database, including 1,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (301 hom., cov: 33)
  • Exomes 𝑓: 0.052 (1588 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0600
• Publications: 9 publications found

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]

PARK7 Gene-Disease associations (from GenCC):

• Parkinson disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive early-onset Parkinson disease 7

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-7970796-G-A is Benign according to our data. Variant chr1-7970796-G-A is described in ClinVar as Benign. ClinVar VariationId is 1227703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007262.5. 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
	PARK7	NM_007262.5	MANE Select	c.253-98G>A		intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.253-98G>A		intron	N/A	NP_001116849.1	Q99497

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARK7	ENST00000338639.10	TSL:1 MANE Select	c.253-98G>A		intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.253-98G>A		intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000923305.1		c.253-98G>A		intron	N/A	ENSP00000593364.1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9211 AN: 152120 Hom.: 302 Cov.: 33

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0540

Gnomad OTH AF: 0.0630

GnomAD4 exome AF: 0.0516 AC: 50082 AN: 970186 Hom.: 1588 AF XY: 0.0535 AC XY: 26680 AN XY: 498524

African (AFR) AF: 0.0898 AC: 2108 AN: 23472

American (AMR) AF: 0.0270 AC: 1004 AN: 37230

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 1452 AN: 22622

East Asian (EAS) AF: 0.00130 AC: 46 AN: 35434

South Asian (SAS) AF: 0.0871 AC: 6308 AN: 72458

European-Finnish (FIN) AF: 0.0550 AC: 2760 AN: 50162

Middle Eastern (MID) AF: 0.0662 AC: 221 AN: 3336

European-Non Finnish (NFE) AF: 0.0495 AC: 33776 AN: 681658

Other (OTH) AF: 0.0549 AC: 2407 AN: 43814

GnomAD4 genome AF: 0.0606 AC: 9222 AN: 152238 Hom.: 301 Cov.: 33 AF XY: 0.0601 AC XY: 4475 AN XY: 74448

African (AFR) AF: 0.0861 AC: 3574 AN: 41524

American (AMR) AF: 0.0386 AC: 590 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.0902 AC: 435 AN: 4824

European-Finnish (FIN) AF: 0.0517 AC: 548 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0540 AC: 3673 AN: 68018

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0604 Hom.: 50

Bravo AF: 0.0580

Asia WGS AF: 0.0640 AC: 225 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.060
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: rs6703670; hg19: chr1-8030856;