3-49641218-A-G

Variant names:

• chr3-49641218-A-G
• rs4283605
• NM_003458.4:c.634-1050A>G

Variant summary

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

The NM_003458.4(BSN):​c.634-1050A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,008 control chromosomes in the GnomAD database, including 6,479 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 0.28 (6479 hom., cov: 32)
• Consequence: BSN NM_003458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 29 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-AS1 (HGNC:40102): (BSN antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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 rank	MANE	Protein	UniProt
BSN	NM_003458.4	c.634-1050A>G		intron_variant	Intron 2 of 11	ENST00000296452.5	NP_003449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSN	ENST00000296452.5	c.634-1050A>G		intron_variant	Intron 2 of 11	1	NM_003458.4	ENSP00000296452.4
BSN-AS1	ENST00000442384.1	n.150+402T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42668 AN: 151890 Hom.: 6475 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.0455

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.281 AC: 42697 AN: 152008 Hom.: 6479 Cov.: 32 AF XY: 0.283 AC XY: 21005 AN XY: 74298

African (AFR) AF: 0.273 AC: 11292 AN: 41424

American (AMR) AF: 0.208 AC: 3181 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3470

East Asian (EAS) AF: 0.0456 AC: 236 AN: 5170

South Asian (SAS) AF: 0.217 AC: 1044 AN: 4820

European-Finnish (FIN) AF: 0.448 AC: 4738 AN: 10566

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19793 AN: 67972

Other (OTH) AF: 0.286 AC: 604 AN: 2110

Alfa AF: 0.282 Hom.: 9172

Bravo AF: 0.262

Asia WGS AF: 0.135 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.59
PhyloP100		0.32
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: rs4283605; hg19: chr3-49678651;