rs11718165

Positions:

• chr3-49659364-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003458.4(BSN):​c.8641-1122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,046 control chromosomes in the GnomAD database, including 6,031 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6031 hom., cov: 32)
• Consequence: BSN NM_003458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSN	NM_003458.4	c.8641-1122A>G		intron_variant		ENST00000296452.5	NP_003449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSN	ENST00000296452.5	c.8641-1122A>G		intron_variant		1	NM_003458.4	ENSP00000296452	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40882 AN: 151932 Hom.: 6031 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.269 AC: 40895 AN: 152046 Hom.: 6031 Cov.: 32 AF XY: 0.271 AC XY: 20167 AN XY: 74314

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.0436

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.277

Alfa AF: 0.262 Hom.: 928

Bravo AF: 0.249

Asia WGS AF: 0.129 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.84

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: rs11718165; hg19: chr3-49696797;