5-176623953-C-T

Variant names:

• chr5-176623953-C-T
• rs35035889
• NM_003085.5:c.282+2445G>A

Variant summary

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

The NM_003085.5(SNCB):​c.282+2445G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,056 control chromosomes in the GnomAD database, including 2,809 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 0.19 (2809 hom., cov: 32)
• Consequence: SNCB NM_003085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 2 publications found

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]

SNCB Gene-Disease associations (from GenCC):

• Lewy body dementia

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCB	NM_003085.5	c.282+2445G>A		intron_variant	Intron 4 of 5	ENST00000393693.7	NP_003076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCB	ENST00000393693.7	c.282+2445G>A		intron_variant	Intron 4 of 5	1	NM_003085.5	ENSP00000377296.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28397 AN: 151936 Hom.: 2810 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.187 AC: 28414 AN: 152056 Hom.: 2809 Cov.: 32 AF XY: 0.190 AC XY: 14156 AN XY: 74314

African (AFR) AF: 0.161 AC: 6662 AN: 41494

American (AMR) AF: 0.152 AC: 2316 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 758 AN: 3472

East Asian (EAS) AF: 0.322 AC: 1658 AN: 5154

South Asian (SAS) AF: 0.322 AC: 1544 AN: 4802

European-Finnish (FIN) AF: 0.199 AC: 2102 AN: 10570

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12647 AN: 67974

Other (OTH) AF: 0.190 AC: 401 AN: 2110

Alfa AF: 0.164 Hom.: 849

Bravo AF: 0.180

Asia WGS AF: 0.293 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.59
PhyloP100		-0.32
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: rs35035889; hg19: chr5-176050954;