1-7965215-C-T

Variant names:

• chr1-7965215-C-T
• rs7517357
• NM_007262.5:c.91-109C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007262.5(PARK7):​c.91-109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 967,840 control chromosomes in the GnomAD database, including 12,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1686 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10451 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.496
• Publications: 17 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-7965215-C-T is Benign according to our data. Variant chr1-7965215-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARK7	NM_007262.5	MANE Select	c.91-109C>T		intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.91-109C>T		intron	N/A	NP_001116849.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARK7	ENST00000338639.10	TSL:1 MANE Select	c.91-109C>T		intron	N/A	ENSP00000340278.5
	PARK7	ENST00000493678.5	TSL:1	c.91-109C>T		intron	N/A	ENSP00000418770.1
	PARK7	ENST00000377488.5	TSL:3	c.91-109C>T		intron	N/A	ENSP00000366708.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20724 AN: 151844 Hom.: 1681 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.0941

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.151 AC: 123422 AN: 815878 Hom.: 10451 AF XY: 0.148 AC XY: 62880 AN XY: 425782

African (AFR) AF: 0.0817 AC: 1695 AN: 20752

American (AMR) AF: 0.0912 AC: 3208 AN: 35176

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 2089 AN: 21246

East Asian (EAS) AF: 0.0613 AC: 2120 AN: 34558

South Asian (SAS) AF: 0.0923 AC: 6327 AN: 68532

European-Finnish (FIN) AF: 0.266 AC: 11023 AN: 41484

Middle Eastern (MID) AF: 0.0502 AC: 145 AN: 2888

European-Non Finnish (NFE) AF: 0.166 AC: 91719 AN: 552700

Other (OTH) AF: 0.132 AC: 5096 AN: 38542

GnomAD4 genome AF: 0.136 AC: 20735 AN: 151962 Hom.: 1686 Cov.: 32 AF XY: 0.138 AC XY: 10261 AN XY: 74254

African (AFR) AF: 0.0834 AC: 3460 AN: 41464

American (AMR) AF: 0.102 AC: 1556 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3466

East Asian (EAS) AF: 0.0638 AC: 330 AN: 5174

South Asian (SAS) AF: 0.0937 AC: 451 AN: 4812

European-Finnish (FIN) AF: 0.287 AC: 3030 AN: 10540

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11216 AN: 67936

Other (OTH) AF: 0.122 AC: 257 AN: 2106

Alfa AF: 0.156 Hom.: 278

Bravo AF: 0.123

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.28
PhyloP100		-0.50
PromoterAI		0.017	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: rs7517357; hg19: chr1-8025275;