Genetic Variant NM_003458.4:c.*105-36T>C (chr3-49667554-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.935

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

epilepsy
Inheritance: AR, AD Classification: LIMITED Submitted by: G2P

BSN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BSN	NM_003458.4 link	c.*105-36T>C		intron_variant	Intron 11 of 11	ENST00000296452.5	NP_003449.2	Q9UPA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSN	ENST00000296452.5 link	c.*105-36T>C		intron_variant	Intron 11 of 11	1	NM_003458.4	ENSP00000296452.4		Q9UPA5

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76714

AN:

151870

Hom.:

20926

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.418

AC XY:

133

AN XY:

318

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.443

AC:

201

AN:

454

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.450

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.505

AC:

76754

AN:

151988

Hom.:

20941

Cov.:

AF XY:

0.511

AC XY:

37940

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.349

AC:

14443

AN:

41428

American (AMR)

AF:

0.641

AC:

9787

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1407

AN:

3470

East Asian (EAS)

AF:

0.945

AC:

4874

AN:

5156

South Asian (SAS)

AF:

0.719

AC:

3467

AN:

4820

European-Finnish (FIN)

AF:

0.463

AC:

4889

AN:

10566

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.532

AC:

36153

AN:

67956

Other (OTH)

AF:

0.502

AC:

1059

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1808

3615

5423

7230

9038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.532

Hom.:

11181

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

(source)

DANN

Benign

0.70

PhyloP100

0.94

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over