rs2005557

Variant names:

• chr3-49663865-G-A
• rs2005557
• NM_003458.4:c.11587G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 42 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 (MetaRNN=6.6321684E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSN	NM_003458.4	MANE Select	c.11587G>A	p.Ala3863Thr	missense	Exon 8 of 12	NP_003449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSN	ENST00000296452.5	TSL:1 MANE Select	c.11587G>A	p.Ala3863Thr	missense	Exon 8 of 12	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

GnomAD2 exomes AF: 0.594 AC: 148920 AN: 250692 AF XY: 0.593

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 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

African (AFR) AF: 0.418 AC: 13993 AN: 33472

American (AMR) AF: 0.746 AC: 33332 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 10756 AN: 26128

East Asian (EAS) AF: 0.958 AC: 38034 AN: 39700

South Asian (SAS) AF: 0.710 AC: 61259 AN: 86250

European-Finnish (FIN) AF: 0.469 AC: 24968 AN: 53234

Middle Eastern (MID) AF: 0.475 AC: 2739 AN: 5764

European-Non Finnish (NFE) AF: 0.530 AC: 588742 AN: 1111820

Other (OTH) AF: 0.544 AC: 32859 AN: 60390

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

African (AFR) AF: 0.428 AC: 17768 AN: 41484

American (AMR) AF: 0.649 AC: 9916 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4894 AN: 5174

South Asian (SAS) AF: 0.728 AC: 3511 AN: 4826

European-Finnish (FIN) AF: 0.463 AC: 4898 AN: 10574

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36181 AN: 67932

Other (OTH) AF: 0.517 AC: 1090 AN: 2110

Alfa AF: 0.532 Hom.: 66184

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 v4.9

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
PhyloP100		0.40
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
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: rs2005557; hg19: chr3-49701298; COSMIC: COSV56517070;