1-7962111-C-T

Variant names:

• chr1-7962111-C-T
• rs226250
• NM_007262.5:c.-24+318C>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.-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
• 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=-0.9).
• BP6: Variant 1-7962111-C-T is Benign according to our data. Variant chr1-7962111-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.-24+318C>T		intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.-24+376C>T		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.-24+318C>T		intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-24+376C>T		intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000872631.1		c.-675C>T		5_prime_UTR	Exon 1 of 6	ENSP00000542690.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.0714 AC: 1 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 36

South Asian (SAS) AF: 0.273 AC: 6 AN: 22

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.386 AC: 128 AN: 332

Other (OTH) AF: 0.333 AC: 2 AN: 6

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

African (AFR) AF: 0.0715 AC: 2970 AN: 41512

American (AMR) AF: 0.261 AC: 3990 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5180

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4816

European-Finnish (FIN) AF: 0.334 AC: 3519 AN: 10530

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27785 AN: 67964

Other (OTH) AF: 0.296 AC: 625 AN: 2112

Alfa AF: 0.146 Hom.: 334

Bravo AF: 0.262

Asia WGS AF: 0.114 AC: 395 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.82
PhyloP100		0.17
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs226250; hg19: chr1-8022171;