Genetic Variant CBLN2:c.-166-77G>A (chr18-72542403-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182511.4(CBLN2):c.-166-77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 235,298 control chromosomes in the GnomAD database, including 1,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 887 hom., cov: 31)

Exomes 𝑓: 0.044 ( 337 hom. )

Consequence

CBLN2
NM_182511.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.693

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 18-72542403-C-T is Benign according to our data. Variant chr18-72542403-C-T is described in ClinVar as Benign. ClinVar VariationId is 1179251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182511.4. 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
	CBLN2	NM_182511.4	MANE Select	c.-166-77G>A		intron	N/A	NP_872317.1	Q8IUK8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CBLN2	ENST00000269503.9	TSL:1 MANE Select	c.-166-77G>A	intron	N/A	ENSP00000269503.4	Q8IUK8
CBLN2	ENST00000585159.5	TSL:1	c.-166-77G>A	intron	N/A	ENSP00000463771.1	Q8IUK8
CBLN2	ENST00000881350.1		c.-243G>A	5_prime_UTR	Exon 1 of 3	ENSP00000551409.1

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7879

AN:

151956

Hom.:

885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0452

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.0895

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0298

Gnomad OTH

AF:

0.0508

GnomAD4 exome

AF:

0.0439

AC:

3655

AN:

83226

Hom.:

337

AF XY:

0.0423

AC XY:

1851

AN XY:

43768

show subpopulations

African (AFR)

AF:

0.0144

AC:

AN:

1740

American (AMR)

AF:

0.0312

AC:

AN:

2504

Ashkenazi Jewish (ASJ)

AF:

0.0140

AC:

AN:

2786

East Asian (EAS)

AF:

0.393

AC:

1375

AN:

3502

South Asian (SAS)

AF:

0.0554

AC:

AN:

722

European-Finnish (FIN)

AF:

0.0751

AC:

618

AN:

8228

Middle Eastern (MID)

AF:

0.0153

AC:

AN:

458

European-Non Finnish (NFE)

AF:

0.0211

AC:

1226

AN:

58112

Other (OTH)

AF:

0.0477

AC:

247

AN:

5174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

102

203

305

406

508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0519

AC:

7885

AN:

152072

Hom.:

887

Cov.:

AF XY:

0.0587

AC XY:

4363

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0156

AC:

650

AN:

41548

American (AMR)

AF:

0.0452

AC:

691

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

AN:

3472

East Asian (EAS)

AF:

0.537

AC:

2697

AN:

5026

South Asian (SAS)

AF:

0.0898

AC:

432

AN:

4810

European-Finnish (FIN)

AF:

0.106

AC:

1128

AN:

10614

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0298

AC:

2025

AN:

67988

Other (OTH)

AF:

0.0517

AC:

109

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

304

608

912

1216

1520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0350

Hom.:

Bravo

AF:

0.0488

Asia WGS

AF:

0.236

AC:

817

AN:

3470

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.9

(source)

DANN

Benign

0.75

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over