1-7961850-G-GGTGCTGGACGGTGTCCCT

Variant names:

• chr1-7961850-G-GGTGCTGGACGGTGTCCCT
• rs200968609
• NM_007262.5:c.-24+75_-24+92dupTGTGCTGGACGGTGTCCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007262.5(PARK7):​c.-24+75_-24+92dupTGTGCTGGACGGTGTCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 151,970 control chromosomes in the GnomAD database, including 81 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (81 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.222
• Publications: 7 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 -10 ACMG points.

• BP6: Variant 1-7961850-G-GGTGCTGGACGGTGTCCCT is Benign according to our data. Variant chr1-7961850-G-GGTGCTGGACGGTGTCCCT is described in ClinVar as Benign. ClinVar VariationId is 487088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 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.-24+75_-24+92dupTGTGCTGGACGGTGTCCC		intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.-24+133_-24+150dupTGTGCTGGACGGTGTCCC		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.-24+75_-24+92dupTGTGCTGGACGGTGTCCC		intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-24+133_-24+150dupTGTGCTGGACGGTGTCCC		intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000872631.1		c.-918_-901dupTGTGCTGGACGGTGTCCC		5_prime_UTR	Exon 1 of 6	ENSP00000542690.1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2836 AN: 151854 Hom.: 81 Cov.: 30

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0134

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 272 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 182

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 10

South Asian (SAS) AF: 0.00 AC: 0 AN: 16

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 212

Other (OTH) AF: 0.00 AC: 0 AN: 14

GnomAD4 genome AF: 0.0186 AC: 2834 AN: 151970 Hom.: 81 Cov.: 30 AF XY: 0.0186 AC XY: 1380 AN XY: 74274

African (AFR) AF: 0.0594 AC: 2460 AN: 41440

American (AMR) AF: 0.00817 AC: 125 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5158

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67934

Other (OTH) AF: 0.0133 AC: 28 AN: 2110

Alfa AF: 0.00 Hom.: 105

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200968609; hg19: chr1-8021910;