Variant 18-72542086-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182511.4(CBLN2):c.75G>T(p.Pro25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 1,532,654 control chromosomes in the GnomAD database, including 613,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.72 ( 45241 hom., cov: 32)

Exomes 𝑓: 0.90 ( 568402 hom. )

Consequence

CBLN2
NM_182511.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.984

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]

CBLN2 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 (BayesDel_noAF=-0.35).

BP6

Variant 18-72542086-C-A is Benign according to our data. Variant chr18-72542086-C-A is described in ClinVar as [Benign]. Clinvar id is 1250060.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.984 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4 linkuse as main transcript	c.75G>T	p.Pro25=	synonymous_variant	3/5	ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9 linkuse as main transcript	c.75G>T	p.Pro25=	synonymous_variant	3/5	1	NM_182511.4	P1

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108509

AN:

151596

Hom.:

45233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.925

Gnomad AMR

AF:

0.834

Gnomad ASJ

AF:

0.920

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.806

Gnomad NFE

AF:

0.937

Gnomad OTH

AF:

0.758

GnomAD3 exomes

AF:

0.853

AC:

134572

AN:

157814

Hom.:

59436

AF XY:

0.855

AC XY:

76896

AN XY:

89988

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.901

Gnomad ASJ exome

AF:

0.923

Gnomad EAS exome

AF:

0.412

Gnomad SAS exome

AF:

0.748

Gnomad FIN exome

AF:

0.906

Gnomad NFE exome

AF:

0.941

Gnomad OTH exome

AF:

0.888

GnomAD4 exome

AF:

0.897

AC:

1238976

AN:

1380948

Hom.:

568402

Cov.:

AF XY:

0.895

AC XY:

613236

AN XY:

685300

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.891

Gnomad4 ASJ exome

AF:

0.922

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.741

Gnomad4 FIN exome

AF:

0.898

Gnomad4 NFE exome

AF:

0.942

Gnomad4 OTH exome

AF:

0.848

GnomAD4 genome

AF:

0.715

AC:

108535

AN:

151706

Hom.:

45241

Cov.:

AF XY:

0.713

AC XY:

52838

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.283

Gnomad4 AMR

AF:

0.834

Gnomad4 ASJ

AF:

0.920

Gnomad4 EAS

AF:

0.377

Gnomad4 SAS

AF:

0.698

Gnomad4 FIN

AF:

0.891

Gnomad4 NFE

AF:

0.937

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.840

Hom.:

9697

Bravo

AF:

0.692

Asia WGS

AF:

0.552

AC:

1913

AN:

3464

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 submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.4

DANN

Benign

0.90

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