rs6446285

Variant names:

• chr3-49588873-G-A
• rs6446285
• NM_003458.4:c.224+34047G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003458.4(BSN):​c.224+34047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 151,966 control chromosomes in the GnomAD database, including 58,024 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 0.87 (58024 hom., cov: 30)
• Consequence: BSN NM_003458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 9 publications found

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]

BSN Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AR, AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSN	NM_003458.4	c.224+34047G>A		intron_variant	Intron 1 of 11	ENST00000296452.5	NP_003449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSN	ENST00000296452.5	c.224+34047G>A		intron_variant	Intron 1 of 11	1	NM_003458.4	ENSP00000296452.4

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132551 AN: 151848 Hom.: 57971 Cov.: 30

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.873 AC: 132662 AN: 151966 Hom.: 58024 Cov.: 30 AF XY: 0.878 AC XY: 65250 AN XY: 74290

African (AFR) AF: 0.888 AC: 36823 AN: 41488

American (AMR) AF: 0.897 AC: 13695 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3031 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5134 AN: 5176

South Asian (SAS) AF: 0.948 AC: 4575 AN: 4824

European-Finnish (FIN) AF: 0.915 AC: 9573 AN: 10468

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57043 AN: 67956

Other (OTH) AF: 0.855 AC: 1806 AN: 2112

Alfa AF: 0.859 Hom.: 9733

Bravo AF: 0.870

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.90
DANN	Benign	0.34
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6446285; hg19: chr3-49626306;