Variant 3-49663865-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.403

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.11587G>A	p.Ala3863Thr	missense_variant	8/12	ENST00000296452.5	NP_003449.2	Q9UPA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSN	ENST00000296452.5 linkuse as main transcript	c.11587G>A	p.Ala3863Thr	missense_variant	8/12	1	NM_003458.4	ENSP00000296452.4		Q9UPA5

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

80290

AN:

151946

Hom.:

22394

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.556

AC XY:

404339

AN XY:

727066

show subpopulations

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.:

AF XY:

0.534

AC XY:

39696

AN XY:

74344

show subpopulations

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.8

DANN

Benign

0.84

DEOGEN2

Benign

0.11

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0089

LIST_S2

Benign

0.11

MetaRNN

Benign

6.6e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.38

PROVEAN

Benign

0.29

REVEL

Benign

0.042

Sift

Benign

1.0

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.013

MPC

0.28

ClinPred

0.0077

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over