5-176626335-GGTGT-G

Position:

• chr5-176626335-GGTGT-G

Variant summary

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

The NM_003085.5(SNCB):​c.282+59_282+62del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 741,658 control chromosomes in the GnomAD database, including 23,500 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11595 hom., cov: 0)
  • Exomes 𝑓: 0.47 (11905 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-GGTGT-G is Benign according to our data. Variant chr5-176626335-GGTGT-G is described in ClinVar as [Benign]. Clinvar id is 1253251.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCB	NM_003085.5	c.282+59_282+62del		intron_variant		ENST00000393693.7	NP_003076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCB	ENST00000393693.7	c.282+59_282+62del		intron_variant		1	NM_003085.5	ENSP00000377296	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 53950 AN: 148902 Hom.: 11583 Cov.: 0

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.475 AC: 281349 AN: 592658 Hom.: 11905 AF XY: 0.474 AC XY: 148999 AN XY: 314172

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.363

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.362 AC: 53985 AN: 149000 Hom.: 11595 Cov.: 0 AF XY: 0.357 AC XY: 25908 AN XY: 72632

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.0205

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.383

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

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;