chr3-49597263-G-A

Position:

• chr3-49597263-G-A

Variant summary

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

The NM_003458.4(BSN):​c.225-27712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,844 control chromosomes in the GnomAD database, including 6,771 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 0.29 (6771 hom., cov: 32)
• Consequence: BSN NM_003458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSN	NM_003458.4	c.225-27712G>A		intron_variant		ENST00000296452.5	NP_003449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSN	ENST00000296452.5	c.225-27712G>A		intron_variant		1	NM_003458.4	ENSP00000296452	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43499 AN: 151726 Hom.: 6766 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.0580

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.287 AC: 43526 AN: 151844 Hom.: 6771 Cov.: 32 AF XY: 0.289 AC XY: 21435 AN XY: 74198

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.290

Alfa AF: 0.285 Hom.: 1173

Bravo AF: 0.265

Asia WGS AF: 0.141 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.088

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: rs9875617; hg19: chr3-49634696;