rs6879864

Variant names:

• chr5-176629805-C-A
• NM_003085.5:c.-9-142G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-176629805-C-A
• chr5-176629805-C-T

Variant summary

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

The NM_001001502.3(SNCB):​c.-10+4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000991 in 1,008,876 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: 9.9e-7 (0 hom.)
• Consequence: SNCB NM_001001502.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001992
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

Genes affected

SNCB (HGNC:11140): (synuclein beta) This gene encodes a member of a small family of proteins that inhibit phospholipase D2 and may function in neuronal plasticity. The encoded protein is abundant in lesions of patients with Alzheimer disease. A mutation in this gene was found in individuals with dementia with Lewy bodies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCB	NM_003085.5	c.-9-142G>T		intron_variant	Intron 1 of 5	ENST00000393693.7	NP_003076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCB	ENST00000393693.7	c.-9-142G>T		intron_variant	Intron 1 of 5	1	NM_003085.5	ENSP00000377296.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 9.91e-7 AC: 1 AN: 1008876 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 497212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000128

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-176056806;