rs2197120

Variant names:

• chr4-89808451-A-G
• rs2197120
• NM_000345.4:c.306+13795T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-89808451-A-G
• chr4-89808451-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000345.4(SNCA):​c.306+13795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,058 control chromosomes in the GnomAD database, including 46,540 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 0.78 (46540 hom., cov: 32)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant Parkinson disease 4

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Parkinson disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• autosomal dominant Parkinson disease 1

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• Lewy body dementia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• hereditary late onset Parkinson disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• parkinsonian-pyramidal syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCA	NM_000345.4	c.306+13795T>C		intron_variant	Intron 4 of 5	ENST00000394991.8	NP_000336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000394991.8	c.306+13795T>C		intron_variant	Intron 4 of 5	1	NM_000345.4	ENSP00000378442.4

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118701 AN: 151940 Hom.: 46505 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.776

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.781 AC: 118781 AN: 152058 Hom.: 46540 Cov.: 32 AF XY: 0.778 AC XY: 57811 AN XY: 74326

African (AFR) AF: 0.782 AC: 32458 AN: 41484

American (AMR) AF: 0.734 AC: 11204 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3472

East Asian (EAS) AF: 0.853 AC: 4407 AN: 5168

South Asian (SAS) AF: 0.686 AC: 3302 AN: 4810

European-Finnish (FIN) AF: 0.814 AC: 8590 AN: 10558

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53744 AN: 67984

Other (OTH) AF: 0.773 AC: 1631 AN: 2110

Alfa AF: 0.780 Hom.: 23646

Bravo AF: 0.781

Asia WGS AF: 0.757 AC: 2633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.081
DANN	Benign	0.49
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs2197120; hg19: chr4-90729602;