5-176626335-GGTGTGTGTGTGT-GGTGTGT

Variant names:

• chr5-176626335-GGTGTGT-G
• rs5873543
• NM_003085.5:c.282+57_282+62delACACAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003085.5(SNCB):​c.282+57_282+62delACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 784,714 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: SNCB NM_003085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• 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: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.282+57_282+62delACACAC		intron	N/A	NP_003076.1	Q16143
	SNCB	NM_001001502.3		c.282+57_282+62delACACAC		intron	N/A	NP_001001502.1	Q16143
	SNCB	NM_001363140.2		c.282+57_282+62delACACAC		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.282+57_282+62delACACAC		intron	N/A	ENSP00000377296.2	Q16143
	SNCB	ENST00000310112.7	TSL:1	c.282+57_282+62delACACAC		intron	N/A	ENSP00000308057.3	Q16143
	SNCB	ENST00000614675.4	TSL:1	c.240+57_240+62delACACAC		intron	N/A	ENSP00000479489.1	G4Y816

Frequencies

GnomAD3 genomes AF: 0.000188 AC: 28 AN: 149178 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000669

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.0000983

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000253

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0291 AC: 18475 AN: 635434 Hom.: 0 AF XY: 0.0287 AC XY: 9786 AN XY: 341130

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00476 AC: 89 AN: 18692

American (AMR) AF: 0.0316 AC: 1173 AN: 37088

Ashkenazi Jewish (ASJ) AF: 0.0189 AC: 358 AN: 18942

East Asian (EAS) AF: 0.00115 AC: 38 AN: 33026

South Asian (SAS) AF: 0.00800 AC: 529 AN: 66146

European-Finnish (FIN) AF: 0.0365 AC: 1537 AN: 42148

Middle Eastern (MID) AF: 0.0186 AC: 47 AN: 2526

European-Non Finnish (NFE) AF: 0.0360 AC: 13887 AN: 385346

Other (OTH) AF: 0.0259 AC: 817 AN: 31520

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000188 AC: 28 AN: 149280 Hom.: 0 Cov.: 0 AF XY: 0.000110 AC XY: 8 AN XY: 72794

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000148 AC: 6 AN: 40538

American (AMR) AF: 0.0000668 AC: 1 AN: 14976

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3434

East Asian (EAS) AF: 0.000200 AC: 1 AN: 5010

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4686

European-Finnish (FIN) AF: 0.0000983 AC: 1 AN: 10172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000253 AC: 17 AN: 67202

Other (OTH) AF: 0.00 AC: 0 AN: 2076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000169111), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000218 Hom.: 664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5873543; hg19: chr5-176053336;