5-176626335-GGT-G

Variant names:

• chr5-176626335-GGT-G
• rs5873543
• NM_003085.5:c.282+61_282+62delAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003085.5(SNCB):​c.282+61_282+62delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 856,966 control chromosomes in the GnomAD database, including 32,331 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (24620 hom., cov: 0)
  • Exomes 𝑓: 0.41 (7711 hom.)
• Consequence: SNCB NM_003085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.463

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-176626335-GGT-G is Benign according to our data. Variant chr5-176626335-GGT-G is described in ClinVar as [Benign]. Clinvar id is 1282871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCB	NM_003085.5	c.282+61_282+62delAC		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+61_282+62delAC		intron_variant	Intron 4 of 5	1	NM_003085.5	ENSP00000377296.2

Frequencies

GnomAD3 genomes AF: 0.566 AC: 84435 AN: 149136 Hom.: 24604 Cov.: 0

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.610

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.407 AC: 287883 AN: 707726 Hom.: 7711 AF XY: 0.408 AC XY: 154944 AN XY: 379500

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.566 AC: 84486 AN: 149240 Hom.: 24620 Cov.: 0 AF XY: 0.571 AC XY: 41555 AN XY: 72754

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.966

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.559

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs5873543; hg19: chr5-176053336;