chr1-7962740-C-CT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_007262.5(PARK7):​c.-23-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,138,026 control chromosomes in the GnomAD database, including 36 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (32 hom., cov: 29)
  • Exomes 𝑓: 0.11 (4 hom.)
• 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-C-CT is Benign according to our data. Variant chr1-7962740-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1182033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0201 (2318/115166) while in subpopulation NFE AF = 0.0317 (1676/52842). AF 95% confidence interval is 0.0305. There are 32 homozygotes in GnomAd4. There are 1080 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

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.-23-4dupT		splice_region intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.-23-4dupT		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.-23-4dupT		splice_region intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-23-4dupT		splice_region intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000872631.1		c.-27dupT		5_prime_UTR	Exon 1 of 6	ENSP00000542690.1

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 2318 AN: 115178 Hom.: 32 Cov.: 29

Gnomad AFR AF: 0.00886

Gnomad AMI AF: 0.00723

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00873

Gnomad EAS AF: 0.00419

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0199

GnomAD2 exomes AF: 0.0943 AC: 8487 AN: 89970 AF XY: 0.0925

Gnomad AFR exome AF: 0.0809

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0878

Gnomad EAS exome AF: 0.117

Gnomad FIN exome AF: 0.0660

Gnomad NFE exome AF: 0.0945

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.106 AC: 108731 AN: 1022860 Hom.: 4 Cov.: 0 AF XY: 0.105 AC XY: 54290 AN XY: 517076

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

African (AFR) AF: 0.0692 AC: 1535 AN: 22174

American (AMR) AF: 0.0756 AC: 2062 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 1788 AN: 20206

East Asian (EAS) AF: 0.0856 AC: 2750 AN: 32142

South Asian (SAS) AF: 0.0993 AC: 6314 AN: 63590

European-Finnish (FIN) AF: 0.0768 AC: 2679 AN: 34866

Middle Eastern (MID) AF: 0.0830 AC: 278 AN: 3348

European-Non Finnish (NFE) AF: 0.112 AC: 86791 AN: 775270

Other (OTH) AF: 0.103 AC: 4534 AN: 43990

⚠️ 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: 0.0201 AC: 2318 AN: 115166 Hom.: 32 Cov.: 29 AF XY: 0.0196 AC XY: 1080 AN XY: 55138

African (AFR) AF: 0.00885 AC: 288 AN: 32544

American (AMR) AF: 0.0154 AC: 173 AN: 11220

Ashkenazi Jewish (ASJ) AF: 0.00873 AC: 24 AN: 2750

East Asian (EAS) AF: 0.00420 AC: 16 AN: 3810

South Asian (SAS) AF: 0.0105 AC: 35 AN: 3330

European-Finnish (FIN) AF: 0.0107 AC: 67 AN: 6250

Middle Eastern (MID) AF: 0.0183 AC: 4 AN: 218

European-Non Finnish (NFE) AF: 0.0317 AC: 1676 AN: 52842

Other (OTH) AF: 0.0199 AC: 30 AN: 1510

Alfa AF: 0.0322 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

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;