Variant 3-49651777-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003458.4(BSN):c.2221G>A(p.Ala741Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,612,844 control chromosomes in the GnomAD database, including 69,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.28 ( 6416 hom., cov: 32)

Exomes 𝑓: 0.28 ( 62635 hom. )

Consequence

BSN
NM_003458.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.52

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027731955).

BP6

Variant 3-49651777-G-A is Benign according to our data. Variant chr3-49651777-G-A is described in ClinVar as [Benign]. Clinvar id is 3057088.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSN	NM_003458.4 linkuse as main transcript	c.2221G>A	p.Ala741Thr	missense_variant	5/12	ENST00000296452.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSN	ENST00000296452.5 linkuse as main transcript	c.2221G>A	p.Ala741Thr	missense_variant	5/12	1	NM_003458.4	P1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42478

AN:

151924

Hom.:

6412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.443

Gnomad EAS

AF:

0.0459

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.266

AC:

66161

AN:

248622

Hom.:

10282

AF XY:

0.269

AC XY:

36232

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.0451

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.443

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.284

AC:

415597

AN:

1460802

Hom.:

62635

Cov.:

AF XY:

0.283

AC XY:

205944

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.0436

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.431

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.280

AC:

42507

AN:

152042

Hom.:

6416

Cov.:

AF XY:

0.282

AC XY:

20926

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.443

Gnomad4 EAS

AF:

0.0460

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.290

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.285

Hom.:

10251

Bravo

AF:

0.262

TwinsUK

AF:

0.300

AC:

1114

ALSPAC

AF:

0.285

AC:

1097

ESP6500AA

AF:

0.268

AC:

1179

ESP6500EA

AF:

0.298

AC:

2566

ExAC

AF:

0.263

AC:

31954

Asia WGS

AF:

0.135

AC:

475

AN:

3478

EpiCase

AF:

0.301

EpiControl

AF:

0.296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BSN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.10

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

1.1

REVEL

Benign

0.072

Sift

Benign

0.88

Sift4G

Benign

0.51

Polyphen

0.0030

Vest4

0.062

MPC

0.27

ClinPred

0.0076

GERP RS

4.2

Varity_R

0.033

gMVP

0.10

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over