Genetic Variant ENST00000674129.1:c.-302C>G (chr4-89837238-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000674129.1(SNCA):c.-302C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,620 control chromosomes in the GnomAD database, including 26,089 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 0.58 ( 26009 hom., cov: 28)

Exomes 𝑓: 0.57 ( 80 hom. )

Consequence

SNCA
ENST00000674129.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0270

Publications

23 publications found

Variant links:

Genes affected

SNCA (HGNC:11138): (synuclein alpha) Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2016]

SNCA links:

SNCA-AS1 (HGNC:50600): (SNCA antisense RNA 1)

SNCA-AS1 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=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674129.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
SNCA	NM_001146055.2	c.-26+1014C>G	intron	N/A	NP_001139527.1
SNCA	NM_001375285.1	c.-94-709C>G	intron	N/A	NP_001362214.1
SNCA-AS1	NR_045481.1	n.334+504G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SNCA	ENST00000674129.1		c.-302C>G	5_prime_UTR	Exon 1 of 8	ENSP00000501269.1
SNCA	ENST00000673902.1		c.-302C>G	5_prime_UTR	Exon 1 of 7	ENSP00000501102.1
SNCA	ENST00000336904.7	TSL:2	c.-26+1014C>G	intron	N/A	ENSP00000338345.3

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87329

AN:

151072

Hom.:

25988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.686

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.552

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.552

GnomAD4 exome

AF:

0.570

AC:

244

AN:

428

Hom.:

Cov.:

AF XY:

0.549

AC XY:

180

AN XY:

328

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AF:

0.833

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

AN:

East Asian (EAS)

AF:

0.900

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.583

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.542

AC:

192

AN:

354

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.578

AC:

87390

AN:

151192

Hom.:

26009

Cov.:

AF XY:

0.578

AC XY:

42632

AN XY:

73792

show subpopulations

African (AFR)

AF:

0.686

AC:

28261

AN:

41210

American (AMR)

AF:

0.552

AC:

8405

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1730

AN:

3462

East Asian (EAS)

AF:

0.851

AC:

4259

AN:

5004

South Asian (SAS)

AF:

0.540

AC:

2568

AN:

4758

European-Finnish (FIN)

AF:

0.570

AC:

5951

AN:

10444

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.509

AC:

34469

AN:

67782

Other (OTH)

AF:

0.551

AC:

1157

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1778

3557

5335

7114

8892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.542

Hom.:

2842

Bravo

AF:

0.586

Asia WGS

AF:

0.688

AC:

2389

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.50

PhyloP100

0.027

PromoterAI

0.12

Neutral

(source)

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