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GeneBe

18-72541942-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_182511.4(CBLN2):c.219G>A(p.Ser73=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,607,626 control chromosomes in the GnomAD database, including 5,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 692 hom., cov: 33)
Exomes 𝑓: 0.022 ( 4743 hom. )

Consequence

CBLN2
NM_182511.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.235
Variant links:
Genes affected
CBLN2 (HGNC:1544): (cerebellin 2 precursor) Predicted to be involved in maintenance of synapse structure and spontaneous synaptic transmission. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in extracellular space. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-72541942-C-T is Benign according to our data. Variant chr18-72541942-C-T is described in ClinVar as [Benign]. Clinvar id is 1233144.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.235 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CBLN2NM_182511.4 linkuse as main transcriptc.219G>A p.Ser73= synonymous_variant 3/5 ENST00000269503.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CBLN2ENST00000269503.9 linkuse as main transcriptc.219G>A p.Ser73= synonymous_variant 3/51 NM_182511.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0295
AC:
4482
AN:
152132
Hom.:
691
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00422
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0335
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.493
Gnomad SAS
AF:
0.0470
Gnomad FIN
AF:
0.0649
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00413
Gnomad OTH
AF:
0.0282
GnomAD3 exomes
AF:
0.0537
AC:
12978
AN:
241674
Hom.:
2426
AF XY:
0.0503
AC XY:
6633
AN XY:
131918
show subpopulations
Gnomad AFR exome
AF:
0.00464
Gnomad AMR exome
AF:
0.0360
Gnomad ASJ exome
AF:
0.00292
Gnomad EAS exome
AF:
0.508
Gnomad SAS exome
AF:
0.0304
Gnomad FIN exome
AF:
0.0605
Gnomad NFE exome
AF:
0.00368
Gnomad OTH exome
AF:
0.0266
GnomAD4 exome
AF:
0.0219
AC:
31882
AN:
1455376
Hom.:
4743
Cov.:
31
AF XY:
0.0218
AC XY:
15824
AN XY:
724390
show subpopulations
Gnomad4 AFR exome
AF:
0.00257
Gnomad4 AMR exome
AF:
0.0343
Gnomad4 ASJ exome
AF:
0.00303
Gnomad4 EAS exome
AF:
0.465
Gnomad4 SAS exome
AF:
0.0311
Gnomad4 FIN exome
AF:
0.0575
Gnomad4 NFE exome
AF:
0.00380
Gnomad4 OTH exome
AF:
0.0343
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0295
AC:
4485
AN:
152250
Hom.:
692
Cov.:
33
AF XY:
0.0351
AC XY:
2613
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.00421
Gnomad4 AMR
AF:
0.0335
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.494
Gnomad4 SAS
AF:
0.0470
Gnomad4 FIN
AF:
0.0649
Gnomad4 NFE
AF:
0.00413
Gnomad4 OTH
AF:
0.0298
Alfa
AF:
0.00807
Hom.:
30
Bravo
AF:
0.0287
Asia WGS
AF:
0.200
AC:
694
AN:
3478
EpiCase
AF:
0.00305
EpiControl
AF:
0.00267

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
12
Dann
Benign
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs17853471; hg19: chr18-70209177; COSMIC: COSV54050102; COSMIC: COSV54050102; API