rs34762726

Variant names:

• chr3-49651777-G-A
• rs34762726
• NM_003458.4:c.2221G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (6416 hom., cov: 32)
  • Exomes 𝑓: 0.28 (62635 hom.)
• Consequence: BSN NM_003458.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.52
• 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSN	NM_003458.4	MANE Select	c.2221G>A	p.Ala741Thr	missense	Exon 5 of 12	NP_003449.2	Q9UPA5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSN	ENST00000296452.5	TSL:1 MANE Select	c.2221G>A	p.Ala741Thr	missense	Exon 5 of 12	ENSP00000296452.4	Q9UPA5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42478 AN: 151924 Hom.: 6412 Cov.: 32

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

GnomAD2 exomes AF: 0.266 AC: 66161 AN: 248622 AF XY: 0.269

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 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.: 45 AF XY: 0.283 AC XY: 205944 AN XY: 726714

African (AFR) AF: 0.273 AC: 9130 AN: 33476

American (AMR) AF: 0.158 AC: 7051 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11506 AN: 26124

East Asian (EAS) AF: 0.0436 AC: 1729 AN: 39696

South Asian (SAS) AF: 0.234 AC: 20162 AN: 86236

European-Finnish (FIN) AF: 0.431 AC: 22707 AN: 52648

Middle Eastern (MID) AF: 0.304 AC: 1718 AN: 5650

European-Non Finnish (NFE) AF: 0.292 AC: 324190 AN: 1111918

Other (OTH) AF: 0.288 AC: 17404 AN: 60362

GnomAD4 genome AF: 0.280 AC: 42507 AN: 152042 Hom.: 6416 Cov.: 32 AF XY: 0.282 AC XY: 20926 AN XY: 74328

African (AFR) AF: 0.272 AC: 11263 AN: 41480

American (AMR) AF: 0.207 AC: 3164 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3470

East Asian (EAS) AF: 0.0460 AC: 238 AN: 5172

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4810

European-Finnish (FIN) AF: 0.447 AC: 4725 AN: 10578

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19674 AN: 67930

Other (OTH) AF: 0.284 AC: 599 AN: 2106

Alfa AF: 0.283 Hom.: 14147

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	BSN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.65
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.5
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.072
Sift	Benign	0.88	T
Sift4G	Benign	0.51	T
Polyphen		0.0030	B
Vest4		0.062
MPC		0.27
ClinPred		0.0076	T
GERP RS		4.2
Varity_R		0.033
gMVP		0.10
Mutation Taster		=92/8	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: rs34762726; hg19: chr3-49689210; COSMIC: COSV107364574; COSMIC: COSV107364574;