rs2005557

Positions:

• chr3-49663865-G-A
• chr3-49663865-G-C

Variant summary

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

The NM_003458.4(BSN):​c.11587G>A​(p.Ala3863Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,613,530 control chromosomes in the GnomAD database, including 252,776 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.53 (22414 hom., cov: 33)
  • Exomes 𝑓: 0.55 (230362 hom.)
• Consequence: BSN NM_003458.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403

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 (MetaRNN=6.6321684E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSN	NM_003458.4	c.11587G>A	p.Ala3863Thr	missense_variant	8/12	ENST00000296452.5	NP_003449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSN	ENST00000296452.5	c.11587G>A	p.Ala3863Thr	missense_variant	8/12	1	NM_003458.4	ENSP00000296452.4

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80290 AN: 151946 Hom.: 22394 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.512

GnomAD3 exomes AF: 0.594 AC: 148920 AN: 250692 Hom.: 47331 AF XY: 0.593 AC XY: 80425 AN XY: 135514

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.759

Gnomad ASJ exome AF: 0.409

Gnomad EAS exome AF: 0.950

Gnomad SAS exome AF: 0.717

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.552 AC: 806682 AN: 1461466 Hom.: 230362 Cov.: 56 AF XY: 0.556 AC XY: 404339 AN XY: 727066

Gnomad4 AFR exome AF: 0.418

Gnomad4 AMR exome AF: 0.746

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.958

Gnomad4 SAS exome AF: 0.710

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.530

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.528 AC: 80348 AN: 152064 Hom.: 22414 Cov.: 33 AF XY: 0.534 AC XY: 39696 AN XY: 74344

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.517

Alfa AF: 0.532 Hom.: 37945

Bravo AF: 0.534

TwinsUK AF: 0.521 AC: 1932

ALSPAC AF: 0.523 AC: 2017

ESP6500AA AF: 0.432 AC: 1903

ESP6500EA AF: 0.517 AC: 4443

ExAC AF: 0.589 AC: 71544

Asia WGS AF: 0.810 AC: 2811 AN: 3478

EpiCase AF: 0.515

EpiControl AF: 0.514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.8
DANN	Benign	0.84
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	6.6e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.042
Sift	Benign	1.0	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.013
MPC		0.28
ClinPred		0.0077	T
GERP RS		1.3
Varity_R		0.034
gMVP		0.074

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: rs2005557; hg19: chr3-49701298; COSMIC: COSV56517070;