rs759806020

chr3-49656921-CCAGCAGCTGCAG-Cchr3-49656921-CCAGCAGCTGCAG-CCAGCAGCTGCAGCAGCAGCTGCAG

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM4 PP3 BS2

The NM_003458.4(BSN):c.7386_7397del(p.Gln2463_Leu2466del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,598,630 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: BSN NM_003458.4 inframe_deletion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.80

Genes affected

BSN (HGNC:1117): (bassoon presynaptic cytomatrix protein) Neurotransmitters are released from a specific site in the axon terminal called the active zone, which is composed of synaptic vesicles and a meshwork of cytoskeleton underlying the plasma membrane. The protein encoded by this gene is thought to be a scaffolding protein involved in organizing the presynaptic cytoskeleton. The gene is expressed primarily in neurons in the brain. A similar gene product in rodents is concentrated in the active zone of axon terminals and tightly associated with cytoskeletal structures, and is essential for regulating neurotransmitter release from a subset of synapses. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_003458.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BS2: High AC in GnomAd at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSN	NM_003458.4	c.7386_7397del	p.Gln2463_Leu2466del	inframe_deletion	5/12	ENST00000296452.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSN	ENST00000296452.5	c.7386_7397del	p.Gln2463_Leu2466del	inframe_deletion	5/12	1	NM_003458.4	P1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000176 AC: 39 AN: 221864 Hom.: 1 AF XY: 0.000164 AC XY: 20 AN XY: 121804

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.000374

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000197

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000197 AC: 285 AN: 1446304 Hom.: 1 AF XY: 0.000188 AC XY: 135 AN XY: 717904

Gnomad4 AFR exome AF: 0.000151

Gnomad4 AMR exome AF: 0.000280

Gnomad4 ASJ exome AF: 0.0000774

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000177

Gnomad4 FIN exome AF: 0.0000195

Gnomad4 NFE exome AF: 0.000208

Gnomad4 OTH exome AF: 0.000302

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74480

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.000155

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum Uncertain:1

Uncertain significance, no assertion criteria provided

research

CHU Sainte-Justine Research Center, University of Montreal

Aug 12, 2016

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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: rs759806020; hg19: chr3-49694354;