rs11548933

Variant names:

• chr1-7962764-C-A
• rs11548933
• NM_007262.5:c.-22C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-7962764-C-A
• chr1-7962764-C-G
• chr1-7962764-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007262.5(PARK7):​c.-22C>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,105,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: PARK7 NM_007262.5 splice_region
• Scores: Splicing: ADA: 0.00005620
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.-22C>A		splice_region	Exon 2 of 7	NP_009193.2
	PARK7	NM_007262.5	MANE Select	c.-22C>A		5_prime_UTR	Exon 2 of 7	NP_009193.2
	PARK7	NM_001123377.2		c.-22C>A		splice_region	Exon 2 of 7	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.-22C>A		splice_region	Exon 2 of 7	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-22C>A		splice_region	Exon 2 of 7	ENSP00000418770.1	Q99497
	PARK7	ENST00000338639.10	TSL:1 MANE Select	c.-22C>A		5_prime_UTR	Exon 2 of 7	ENSP00000340278.5	Q99497

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000353 AC: 39 AN: 1105216 Hom.: 0 Cov.: 20 AF XY: 0.0000338 AC XY: 19 AN XY: 561570

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

African (AFR) AF: 0.0000375 AC: 1 AN: 26648

American (AMR) AF: 0.00 AC: 0 AN: 37840

Ashkenazi Jewish (ASJ) AF: 0.0000452 AC: 1 AN: 22118

East Asian (EAS) AF: 0.00 AC: 0 AN: 35226

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3414

European-Non Finnish (NFE) AF: 0.0000405 AC: 33 AN: 815798

Other (OTH) AF: 0.0000635 AC: 3 AN: 47214

⚠️ 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 Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.43
PhyloP100		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000056
dbscSNV1_RF	Benign	0.012
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: rs11548933; hg19: chr1-8022824;