1-7962740-CTTTTTTTT-CTTTTTTT

Variant names:

• chr1-7962740-CT-C
• rs370370394
• NM_007262.5:c.-23-4delT

Variant summary

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

The NM_007262.5(PARK7):​c.-23-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 115,136 control chromosomes in the GnomAD database, including 496 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (496 hom., cov: 29)
  • Exomes 𝑓: 0.29 (19 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARK7 NM_007262.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11
• Publications: 1 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 1-7962740-CT-C is Benign according to our data. Variant chr1-7962740-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1234017.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 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.-23-4delT		splice_region intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.-23-4delT		splice_region 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.-23-4delT		splice_region intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-23-4delT		splice_region intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000872631.1		c.-27delT		5_prime_UTR	Exon 1 of 6	ENSP00000542690.1

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 7016 AN: 115148 Hom.: 496 Cov.: 29

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00145

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.00400

Gnomad EAS AF: 0.00157

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.00651

Gnomad OTH AF: 0.0532

GnomAD2 exomes AF: 0.360 AC: 32426 AN: 89970 AF XY: 0.363

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.350

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.288 AC: 288040 AN: 999166 Hom.: 19 Cov.: 0 AF XY: 0.291 AC XY: 146686 AN XY: 503940

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.328 AC: 7179 AN: 21880

American (AMR) AF: 0.282 AC: 7446 AN: 26442

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 6156 AN: 19456

East Asian (EAS) AF: 0.312 AC: 9706 AN: 31108

South Asian (SAS) AF: 0.308 AC: 18902 AN: 61402

European-Finnish (FIN) AF: 0.282 AC: 9599 AN: 34070

Middle Eastern (MID) AF: 0.287 AC: 931 AN: 3240

European-Non Finnish (NFE) AF: 0.284 AC: 215445 AN: 758590

Other (OTH) AF: 0.295 AC: 12676 AN: 42978

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0610 AC: 7024 AN: 115136 Hom.: 496 Cov.: 29 AF XY: 0.0618 AC XY: 3409 AN XY: 55122

African (AFR) AF: 0.186 AC: 6046 AN: 32522

American (AMR) AF: 0.0312 AC: 350 AN: 11218

Ashkenazi Jewish (ASJ) AF: 0.00400 AC: 11 AN: 2752

East Asian (EAS) AF: 0.00157 AC: 6 AN: 3810

South Asian (SAS) AF: 0.0192 AC: 64 AN: 3328

European-Finnish (FIN) AF: 0.0179 AC: 112 AN: 6250

Middle Eastern (MID) AF: 0.0459 AC: 10 AN: 218

European-Non Finnish (NFE) AF: 0.00651 AC: 344 AN: 52838

Other (OTH) AF: 0.0531 AC: 80 AN: 1508

Alfa AF: 0.0791 Hom.: 4

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		1.1
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: rs370370394; hg19: chr1-8022800;