4-89720189-T-C

Position:

• chr4-89720189-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000659878.1(ENSG00000251095):​n.480-6195T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 150,538 control chromosomes in the GnomAD database, including 23,127 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 0.54 (23127 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: ENST00000659878.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124900602	XR_007058466.1	n.10150-84T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000659878.1	n.480-6195T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.542 AC: 81496 AN: 150426 Hom.: 23120 Cov.: 30

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.537

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.542 AC: 81531 AN: 150538 Hom.: 23127 Cov.: 30 AF XY: 0.543 AC XY: 39903 AN XY: 73508

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.536

Alfa AF: 0.614 Hom.: 63686

Bravo AF: 0.517

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs356220; hg19: chr4-90641340;