1-7962111-C-T

Position:

• chr1-7962111-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007262.5(PARK7):​c.-24+318C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,486 control chromosomes in the GnomAD database, including 7,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7739 hom., cov: 32)
  • Exomes 𝑓: 0.33 (28 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.170

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-7962111-C-T is Benign according to our data. Variant chr1-7962111-C-T is described in ClinVar as [Benign]. Clinvar id is 1233736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARK7	NM_007262.5	c.-24+318C>T		intron_variant		ENST00000338639.10	NP_009193.2
PARK7	NM_001123377.2	c.-24+376C>T		intron_variant			NP_001116849.1
PARK7	XM_005263424.4	c.-24+30C>T		intron_variant			XP_005263481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10	c.-24+318C>T		intron_variant		1	NM_007262.5	ENSP00000340278	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42117 AN: 151948 Hom.: 7737 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.333 AC: 140 AN: 420 Hom.: 28 Cov.: 0 AF XY: 0.343 AC XY: 98 AN XY: 286

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0714

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.277 AC: 42110 AN: 152066 Hom.: 7739 Cov.: 32 AF XY: 0.272 AC XY: 20184 AN XY: 74334

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.296

Alfa AF: 0.146 Hom.: 334

Bravo AF: 0.262

Asia WGS AF: 0.114 AC: 395 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs226250; hg19: chr1-8022171;