chr1-7969450-G-C

Position:

• chr1-7969450-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007262.5(PARK7):​c.252+46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000628 in 596,930 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARK7	NM_007262.5	c.252+46G>C		intron_variant		ENST00000338639.10	NP_009193.2
PARK7	NM_001123377.2	c.252+46G>C		intron_variant			NP_001116849.1
PARK7	XM_005263424.4	c.252+46G>C		intron_variant			XP_005263481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10	c.252+46G>C		intron_variant		1	NM_007262.5	ENSP00000340278.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.000628 AC: 375 AN: 596930 Hom.: 0 Cov.: 10 AF XY: 0.000582 AC XY: 186 AN XY: 319810

Gnomad4 AFR exome AF: 0.0000411

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000424

Gnomad4 EAS exome AF: 0.0000877

Gnomad4 SAS exome AF: 0.0000930

Gnomad4 FIN exome AF: 0.0000467

Gnomad4 NFE exome AF: 0.00100

Gnomad4 OTH exome AF: 0.000316

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.020
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs2641117; hg19: chr1-8029510;