chr5-176626335-G-GGT

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003085.5(SNCB):​c.282+61_282+62dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 864,248 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 0)
  • Exomes 𝑓: 0.00074 (0 hom.)
• Consequence: SNCB NM_003085.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 443 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCB	NM_003085.5	c.282+61_282+62dupAC		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+62_282+63insAC		intron_variant	Intron 4 of 5	1	NM_003085.5	ENSP00000377296.2

Frequencies

GnomAD3 genomes AF: 0.00296 AC: 442 AN: 149342 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00957

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000601

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00339

Gnomad SAS AF: 0.000853

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000327

Gnomad OTH AF: 0.00146

GnomAD4 exome AF: 0.000744 AC: 532 AN: 714802 Hom.: 0 AF XY: 0.000660 AC XY: 253 AN XY: 383244

Gnomad4 AFR exome AF: 0.00891

Gnomad4 AMR exome AF: 0.000579

Gnomad4 ASJ exome AF: 0.0000475

Gnomad4 EAS exome AF: 0.00369

Gnomad4 SAS exome AF: 0.000396

Gnomad4 FIN exome AF: 0.0000211

Gnomad4 NFE exome AF: 0.000290

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00296 AC: 443 AN: 149446 Hom.: 2 Cov.: 0 AF XY: 0.00276 AC XY: 201 AN XY: 72892

Gnomad4 AFR AF: 0.00955

Gnomad4 AMR AF: 0.000600

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00339

Gnomad4 SAS AF: 0.000853

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000327

Gnomad4 OTH AF: 0.00144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;