rs2075667

Variant names:

• chr5-176620760-G-A
• rs2075667
• NM_003085.5:c.*51C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003085.5(SNCB):​c.*51C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 1,348,262 control chromosomes in the GnomAD database, including 10,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.083 (1031 hom., cov: 32)
  • Exomes 𝑓: 0.094 (9409 hom.)
• Consequence: SNCB NM_003085.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.50
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 5-176620760-G-A is Benign according to our data. Variant chr5-176620760-G-A is described in ClinVar as Benign. ClinVar VariationId is 1222753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCB	NM_003085.5	c.*51C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000393693.7	NP_003076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCB	ENST00000393693.7	c.*51C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_003085.5	ENSP00000377296.2

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12591 AN: 152056 Hom.: 1020 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0913

GnomAD2 exomes AF: 0.125 AC: 31388 AN: 250312 AF XY: 0.121

Gnomad AFR exome AF: 0.0394

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.0517

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.0594

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0939 AC: 112360 AN: 1196088 Hom.: 9409 Cov.: 18 AF XY: 0.0938 AC XY: 57003 AN XY: 607656

African (AFR) AF: 0.0402 AC: 1142 AN: 28382

American (AMR) AF: 0.190 AC: 8438 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.0532 AC: 1304 AN: 24508

East Asian (EAS) AF: 0.480 AC: 18746 AN: 39080

South Asian (SAS) AF: 0.148 AC: 12110 AN: 81616

European-Finnish (FIN) AF: 0.120 AC: 6383 AN: 53222

Middle Eastern (MID) AF: 0.107 AC: 552 AN: 5156

European-Non Finnish (NFE) AF: 0.0670 AC: 58138 AN: 867750

Other (OTH) AF: 0.107 AC: 5547 AN: 51940

GnomAD4 genome AF: 0.0829 AC: 12610 AN: 152174 Hom.: 1031 Cov.: 32 AF XY: 0.0903 AC XY: 6719 AN XY: 74380

African (AFR) AF: 0.0391 AC: 1626 AN: 41540

American (AMR) AF: 0.140 AC: 2135 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2347 AN: 5130

South Asian (SAS) AF: 0.154 AC: 744 AN: 4828

European-Finnish (FIN) AF: 0.130 AC: 1373 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0584 AC: 3969 AN: 67986

Other (OTH) AF: 0.0989 AC: 209 AN: 2114

Alfa AF: 0.0664 Hom.: 449

Bravo AF: 0.0843

Asia WGS AF: 0.325 AC: 1126 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.72
PhyloP100		3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2075667; hg19: chr5-176047761; COSMIC: COSV59527496; COSMIC: COSV59527496;