chr3-49667554-T-C

Position:

• chr3-49667554-T-C

Variant summary

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

The NM_003458.4(BSN):​c.*105-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,500 control chromosomes in the GnomAD database, including 20,997 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 0.51 (20941 hom., cov: 31)
  • Exomes 𝑓: 0.45 (56 hom.)
• Consequence: BSN NM_003458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.935

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSN	NM_003458.4	c.*105-36T>C		intron_variant		ENST00000296452.5
BSN	XM_047449149.1	c.*104+2236T>C		intron_variant
BSN	XM_047449150.1	c.*104+2236T>C		intron_variant
BSN	XM_047449152.1	c.*105-36T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSN	ENST00000296452.5	c.*105-36T>C		intron_variant		1	NM_003458.4	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76714 AN: 151870 Hom.: 20926 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.453 AC: 232 AN: 512 Hom.: 56 Cov.: 0 AF XY: 0.418 AC XY: 133 AN XY: 318

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.505 AC: 76754 AN: 151988 Hom.: 20941 Cov.: 31 AF XY: 0.511 AC XY: 37940 AN XY: 74276

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.502

Alfa AF: 0.536 Hom.: 10099

Bravo AF: 0.509

Asia WGS AF: 0.800 AC: 2774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2131109; hg19: chr3-49704987;