1-7965215-C-T

Position:

• chr1-7965215-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARK7	NM_007262.5	c.91-109C>T		intron_variant		ENST00000338639.10
PARK7	NM_001123377.2	c.91-109C>T		intron_variant
PARK7	XM_005263424.4	c.91-109C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARK7	ENST00000338639.10	c.91-109C>T		intron_variant		1	NM_007262.5	P1

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

Gnomad4 AFR exome AF: 0.0817

Gnomad4 AMR exome AF: 0.0912

Gnomad4 ASJ exome AF: 0.0983

Gnomad4 EAS exome AF: 0.0613

Gnomad4 SAS exome AF: 0.0923

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.132

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

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.0937

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.122

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.28

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: rs7517357; hg19: chr1-8025275;