5-176629019-C-T

Variant names:

• chr5-176629019-C-T
• rs4242202
• NM_003085.5:c.121+515G>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.121+515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,764 control chromosomes in the GnomAD database, including 2,313 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 0.16 (2313 hom., cov: 31)
• Consequence: SNCB NM_003085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 3 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: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003085.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCB	NM_003085.5	MANE Select	c.121+515G>A		intron	N/A	NP_003076.1	Q16143
	SNCB	NM_001001502.3		c.121+515G>A		intron	N/A	NP_001001502.1	Q16143
	SNCB	NM_001363140.2		c.121+515G>A		intron	N/A	NP_001350069.1	Q16143

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCB	ENST00000393693.7	TSL:1 MANE Select	c.121+515G>A		intron	N/A	ENSP00000377296.2	Q16143
	SNCB	ENST00000310112.7	TSL:1	c.121+515G>A		intron	N/A	ENSP00000308057.3	Q16143
	SNCB	ENST00000614675.4	TSL:1	c.121+515G>A		intron	N/A	ENSP00000479489.1	G4Y816

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24413 AN: 151646 Hom.: 2313 Cov.: 31

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.161 AC: 24427 AN: 151764 Hom.: 2313 Cov.: 31 AF XY: 0.164 AC XY: 12169 AN XY: 74116

African (AFR) AF: 0.0858 AC: 3549 AN: 41366

American (AMR) AF: 0.135 AC: 2053 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3464

East Asian (EAS) AF: 0.351 AC: 1801 AN: 5124

South Asian (SAS) AF: 0.299 AC: 1439 AN: 4810

European-Finnish (FIN) AF: 0.196 AC: 2059 AN: 10500

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12183 AN: 67956

Other (OTH) AF: 0.171 AC: 359 AN: 2102

Alfa AF: 0.175 Hom.: 3359

Bravo AF: 0.151

Asia WGS AF: 0.288 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.58
PhyloP100		-1.2
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: rs4242202; hg19: chr5-176056020; COSMIC: COSV59436406; COSMIC: COSV59436406;