1-7962764-C-T

Variant names:

• chr1-7962764-C-T
• rs11548933
• NM_007262.5:c.-22C>T

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.-22C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,235,092 control chromosomes in the GnomAD database, including 546 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (289 hom., cov: 29)
  • Exomes 𝑓: 0.0043 (257 hom.)
• Consequence: PARK7 NM_007262.5 splice_region
• Scores: Splicing: ADA: 0.00001403
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.706
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• 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=-0.85).
• BP6: Variant 1-7962764-C-T is Benign according to our data. Variant chr1-7962764-C-T is described in ClinVar as Benign. ClinVar VariationId is 298117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 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.-22C>T		splice_region	Exon 2 of 7	NP_009193.2
	PARK7	NM_007262.5	MANE Select	c.-22C>T		5_prime_UTR	Exon 2 of 7	NP_009193.2
	PARK7	NM_001123377.2		c.-22C>T		splice_region	Exon 2 of 7	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.-22C>T		splice_region	Exon 2 of 7	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-22C>T		splice_region	Exon 2 of 7	ENSP00000418770.1	Q99497
	PARK7	ENST00000338639.10	TSL:1 MANE Select	c.-22C>T		5_prime_UTR	Exon 2 of 7	ENSP00000340278.5	Q99497

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 4959 AN: 129676 Hom.: 288 Cov.: 29

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000489

Gnomad FIN AF: 0.000483

Gnomad MID AF: 0.0122

Gnomad NFE AF: 0.000404

Gnomad OTH AF: 0.0293

GnomAD2 exomes AF: 0.00965 AC: 2136 AN: 221380 AF XY: 0.00712

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.00583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000133

Gnomad NFE exome AF: 0.000331

Gnomad OTH exome AF: 0.00495

GnomAD4 exome AF: 0.00429 AC: 4737 AN: 1105350 Hom.: 257 Cov.: 20 AF XY: 0.00369 AC XY: 2070 AN XY: 561640

African (AFR) AF: 0.143 AC: 3818 AN: 26634

American (AMR) AF: 0.00706 AC: 267 AN: 37818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22114

East Asian (EAS) AF: 0.00 AC: 0 AN: 35224

South Asian (SAS) AF: 0.000295 AC: 22 AN: 74702

European-Finnish (FIN) AF: 0.000213 AC: 9 AN: 42198

Middle Eastern (MID) AF: 0.0103 AC: 35 AN: 3412

European-Non Finnish (NFE) AF: 0.000159 AC: 130 AN: 816026

Other (OTH) AF: 0.00966 AC: 456 AN: 47222

GnomAD4 genome AF: 0.0383 AC: 4966 AN: 129742 Hom.: 289 Cov.: 29 AF XY: 0.0385 AC XY: 2374 AN XY: 61644

African (AFR) AF: 0.134 AC: 4688 AN: 35096

American (AMR) AF: 0.0162 AC: 194 AN: 11948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3234

East Asian (EAS) AF: 0.00 AC: 0 AN: 4542

South Asian (SAS) AF: 0.000491 AC: 2 AN: 4074

European-Finnish (FIN) AF: 0.000483 AC: 3 AN: 6216

Middle Eastern (MID) AF: 0.0135 AC: 3 AN: 222

European-Non Finnish (NFE) AF: 0.000404 AC: 25 AN: 61820

Other (OTH) AF: 0.0291 AC: 51 AN: 1752

Alfa AF: 0.0139 Hom.: 91

Bravo AF: 0.0399

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive early-onset Parkinson disease 7 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.4
DANN	Benign	0.40
PhyloP100		0.71
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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: rs11548933; hg19: chr1-8022824;