rs9858542

chr3-49664550-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_003458.4(BSN):c.11736G>A(p.Thr3912=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,601,082 control chromosomes in the GnomAD database, including 68,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6057 hom., cov: 33)
  • Exomes 𝑓: 0.28 (62085 hom.)
• Consequence: BSN NM_003458.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.510

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-49664550-G-A is Benign according to our data. Variant chr3-49664550-G-A is described in ClinVar as [Benign]. Clinvar id is 3055985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSN	NM_003458.4	c.11736G>A	p.Thr3912=	synonymous_variant	9/12	ENST00000296452.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSN	ENST00000296452.5	c.11736G>A	p.Thr3912=	synonymous_variant	9/12	1	NM_003458.4	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40966 AN: 152072 Hom.: 6057 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.262 AC: 62865 AN: 239664 Hom.: 9655 AF XY: 0.267 AC XY: 34454 AN XY: 129248

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.0438

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.284 AC: 411707 AN: 1448892 Hom.: 62085 Cov.: 37 AF XY: 0.283 AC XY: 203877 AN XY: 719880

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.0385

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.269 AC: 40981 AN: 152190 Hom.: 6057 Cov.: 33 AF XY: 0.272 AC XY: 20214 AN XY: 74396

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.0440

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.279

Alfa AF: 0.284 Hom.: 12509

Bravo AF: 0.249

Asia WGS AF: 0.130 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

BSN-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	0.56
Dann	Benign	0.69

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: rs9858542; hg19: chr3-49701983; COSMIC: COSV56512996;