Variant chr18-72541942-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

CBLN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.235 with no splicing effect.

BA1

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
CBLN2	NM_182511.4 linkuse as main transcript	c.219G>A	p.Ser73=	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.219G>A	p.Ser73=	synonymous_variant	3/5	1	NM_182511.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4482

AN:

152132

Hom.:

691

Cov.:

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.:

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

AF:

0.0295

AC:

4485

AN:

152250

Hom.:

692

Cov.:

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.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

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.

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