rs17411949

Variant summary

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

The NM_022131.3(CLSTN2):​c.233-22778C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 152,222 control chromosomes in the GnomAD database, including 182 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 0.045 ( 182 hom., cov: 32)

Consequence

CLSTN2
NM_022131.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.746

Publications

10 publications found
Variant links:
Genes affected
CLSTN2 (HGNC:17448): (calsyntenin 2) Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of synapse assembly and positive regulation of synaptic transmission. Predicted to be located in postsynaptic density. Predicted to be active in cell surface; glutamatergic synapse; and postsynaptic membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.89).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLSTN2NM_022131.3 linkc.233-22778C>T intron_variant Intron 2 of 16 ENST00000458420.7 NP_071414.2 Q9H4D0
CLSTN2XM_017007022.3 linkc.158-22778C>T intron_variant Intron 2 of 16 XP_016862511.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLSTN2ENST00000458420.7 linkc.233-22778C>T intron_variant Intron 2 of 16 1 NM_022131.3 ENSP00000402460.2 Q9H4D0
CLSTN2ENST00000511524.1 linkn.421-22778C>T intron_variant Intron 2 of 10 2

Frequencies

GnomAD3 genomes
AF:
0.0450
AC:
6840
AN:
152106
Hom.:
177
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0372
Gnomad AMI
AF:
0.0439
Gnomad AMR
AF:
0.0448
Gnomad ASJ
AF:
0.0352
Gnomad EAS
AF:
0.0599
Gnomad SAS
AF:
0.0674
Gnomad FIN
AF:
0.0139
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0520
Gnomad OTH
AF:
0.0550
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0450
AC:
6852
AN:
152222
Hom.:
182
Cov.:
32
AF XY:
0.0439
AC XY:
3265
AN XY:
74410
show subpopulations
African (AFR)
AF:
0.0371
AC:
1543
AN:
41538
American (AMR)
AF:
0.0448
AC:
684
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.0352
AC:
122
AN:
3468
East Asian (EAS)
AF:
0.0599
AC:
310
AN:
5176
South Asian (SAS)
AF:
0.0673
AC:
324
AN:
4816
European-Finnish (FIN)
AF:
0.0139
AC:
147
AN:
10604
Middle Eastern (MID)
AF:
0.0646
AC:
19
AN:
294
European-Non Finnish (NFE)
AF:
0.0520
AC:
3537
AN:
68016
Other (OTH)
AF:
0.0596
AC:
126
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
342
684
1026
1368
1710
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
78
156
234
312
390
<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:
0.0510
Hom.:
693
Bravo
AF:
0.0468
Asia WGS
AF:
0.0910
AC:
316
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.1
DANN
Benign
0.41
PhyloP100
-0.75
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs17411949; hg19: chr3-140099693; API