Genetic Variant NM_007262.5:c.410-2128G>T (chr1-7982766-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007262.5(PARK7):c.410-2128G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,090 control chromosomes in the GnomAD database, including 5,656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5656 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

PARK7
NM_007262.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

22 publications found

Variant links:

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, Labcorp Genetics (formerly Invitae), Ambry Genetics
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PARK7 links:

Y_RNA (HGNC:):

Y_RNA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARK7	NM_007262.5	MANE Select	c.410-2128G>T		intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.410-2128G>T		intron	N/A	NP_001116849.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PARK7	ENST00000338639.10	TSL:1 MANE Select	c.410-2128G>T	intron	N/A	ENSP00000340278.5
PARK7	ENST00000493678.5	TSL:1	c.410-2128G>T	intron	N/A	ENSP00000418770.1
PARK7	ENST00000377488.5	TSL:3	c.410-2128G>T	intron	N/A	ENSP00000366708.1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38016

AN:

151964

Hom.:

5646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.0924

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.219

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.250

AC:

38063

AN:

152082

Hom.:

5656

Cov.:

AF XY:

0.256

AC XY:

19045

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.312

AC:

12931

AN:

41470

American (AMR)

AF:

0.348

AC:

5314

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

419

AN:

3468

East Asian (EAS)

AF:

0.628

AC:

3248

AN:

5168

South Asian (SAS)

AF:

0.134

AC:

647

AN:

4828

European-Finnish (FIN)

AF:

0.293

AC:

3099

AN:

10576

Middle Eastern (MID)

AF:

0.0993

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.174

AC:

11846

AN:

67986

Other (OTH)

AF:

0.219

AC:

462

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1402

2803

4205

5606

7008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.194

Hom.:

6107

Bravo

AF:

0.266

Asia WGS

AF:

0.373

AC:

1296

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

9.6

(source)

DANN

Benign

0.61

PhyloP100

0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over