Genetic Variant SNCB:c.282+55_282+62delACACACAC (chr5-176626335-GGTGTGTGT-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_003085.5(SNCB):c.282+55_282+62delACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 861,488 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), 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 0.000027 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

SNCB
NM_003085.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

2 publications found

Variant links:

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

SNCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNCB	NM_003085.5	MANE Select	c.282+55_282+62delACACACAC	intron	N/A	NP_003076.1	Q16143
SNCB	NM_001001502.3		c.282+55_282+62delACACACAC	intron	N/A	NP_001001502.1	Q16143
SNCB	NM_001363140.2		c.282+55_282+62delACACACAC	intron	N/A	NP_001350069.1	Q16143

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNCB	ENST00000393693.7	TSL:1 MANE Select	c.282+55_282+62delACACACAC	intron	N/A	ENSP00000377296.2	Q16143
SNCB	ENST00000310112.7	TSL:1	c.282+55_282+62delACACACAC	intron	N/A	ENSP00000308057.3	Q16143
SNCB	ENST00000614675.4	TSL:1	c.240+55_240+62delACACACAC	intron	N/A	ENSP00000479489.1	G4Y816

Frequencies

GnomAD3 genomes

AF:

0.0000201

AC:

AN:

149336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000668

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000590

AC:

420

AN:

712048

Hom.:

AF XY:

0.000629

AC XY:

240

AN XY:

381828

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

19194

American (AMR)

AF:

0.000349

AC:

AN:

43030

Ashkenazi Jewish (ASJ)

AF:

0.0000952

AC:

AN:

21010

East Asian (EAS)

AF:

0.0000879

AC:

AN:

34126

South Asian (SAS)

AF:

0.000976

AC:

AN:

70676

European-Finnish (FIN)

AF:

0.000720

AC:

AN:

47196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2760

European-Non Finnish (NFE)

AF:

0.000638

AC:

280

AN:

438744

Other (OTH)

AF:

0.000481

AC:

AN:

35312

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.296

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149440

Hom.:

Cov.:

AF XY:

0.0000412

AC XY:

AN XY:

72888

show subpopulations

African (AFR)

AF:

0.0000247

AC:

AN:

40542

American (AMR)

AF:

0.0000667

AC:

AN:

14994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

5010

South Asian (SAS)

AF:

0.000213

AC:

AN:

4688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67286

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over