rs144768319

Variant names:

• chr1-7962712-CAG-C
• rs144768319
• NM_007262.5:c.-23-50_-23-49delAG

Variant summary

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

The NM_007262.5(PARK7):​c.-23-50_-23-49delAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,246,870 control chromosomes in the GnomAD database, including 17,833 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2895 hom., cov: 25)
  • Exomes 𝑓: 0.15 (14938 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.419
• Publications: 2 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 1-7962712-CAG-C is Benign according to our data. Variant chr1-7962712-CAG-C is described in ClinVar as Benign. ClinVar VariationId is 1289619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 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.-23-50_-23-49delAG		intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.-23-50_-23-49delAG		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.-23-50_-23-49delAG		intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-23-50_-23-49delAG		intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000872631.1		c.-73_-72delAG		5_prime_UTR	Exon 1 of 6	ENSP00000542690.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 27884 AN: 149360 Hom.: 2887 Cov.: 25

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0410

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.0942

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.153 AC: 168202 AN: 1097412 Hom.: 14938 AF XY: 0.150 AC XY: 83551 AN XY: 555436

African (AFR) AF: 0.244 AC: 5962 AN: 24412

American (AMR) AF: 0.0986 AC: 3324 AN: 33698

Ashkenazi Jewish (ASJ) AF: 0.0967 AC: 2211 AN: 22862

East Asian (EAS) AF: 0.0602 AC: 2133 AN: 35458

South Asian (SAS) AF: 0.0936 AC: 6561 AN: 70078

European-Finnish (FIN) AF: 0.259 AC: 10058 AN: 38874

Middle Eastern (MID) AF: 0.0563 AC: 197 AN: 3498

European-Non Finnish (NFE) AF: 0.160 AC: 131054 AN: 820820

Other (OTH) AF: 0.140 AC: 6702 AN: 47712

GnomAD4 genome AF: 0.187 AC: 27915 AN: 149458 Hom.: 2895 Cov.: 25 AF XY: 0.187 AC XY: 13600 AN XY: 72736

African (AFR) AF: 0.259 AC: 10516 AN: 40574

American (AMR) AF: 0.124 AC: 1859 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3464

East Asian (EAS) AF: 0.0644 AC: 328 AN: 5096

South Asian (SAS) AF: 0.0970 AC: 453 AN: 4668

European-Finnish (FIN) AF: 0.283 AC: 2791 AN: 9872

Middle Eastern (MID) AF: 0.101 AC: 29 AN: 286

European-Non Finnish (NFE) AF: 0.166 AC: 11194 AN: 67524

Other (OTH) AF: 0.163 AC: 338 AN: 2068

Alfa AF: 0.189 Hom.: 376

Bravo AF: 0.182

Asia WGS AF: 0.0860 AC: 299 AN: 3478

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		0.42
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: rs144768319; hg19: chr1-8022772; COSMIC: COSV107440740; COSMIC: COSV107440740;