Genetic Variant CBLN2:c.-847+20103G>A (chr18-72618222-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000581073.1(CBLN2):c.15+20103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 227,010 control chromosomes in the GnomAD database, including 2,963 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 0.14 ( 1845 hom., cov: 32)

Exomes 𝑓: 0.15 ( 1118 hom. )

Consequence

CBLN2
ENST00000581073.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

Publications

3 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:

HNRNPA1P11 (HGNC:39129): (heterogeneous nuclear ribonucleoprotein A1 pseudogene 11)

HNRNPA1P11 links:

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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=-0.76).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000581073.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CBLN2	ENST00000971390.1		c.-847+20103G>A	intron	N/A	ENSP00000641449.1
CBLN2	ENST00000581073.1	TSL:4	c.15+20103G>A	intron	N/A	ENSP00000462632.1	J3KST0
CBLN2	ENST00000580889.1	TSL:3	n.104+20130G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20778

AN:

152028

Hom.:

1844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.0484

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0647

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.148

GnomAD4 exome

AF:

0.146

AC:

10953

AN:

74864

Hom.:

1118

Cov.:

AF XY:

0.143

AC XY:

5690

AN XY:

39660

show subpopulations

African (AFR)

AF:

0.0405

AC:

110

AN:

2716

American (AMR)

AF:

0.318

AC:

1366

AN:

4298

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

409

AN:

2118

East Asian (EAS)

AF:

0.00129

AC:

AN:

5414

South Asian (SAS)

AF:

0.0715

AC:

393

AN:

5498

European-Finnish (FIN)

AF:

0.136

AC:

820

AN:

6022

Middle Eastern (MID)

AF:

0.144

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.163

AC:

7194

AN:

44150

Other (OTH)

AF:

0.141

AC:

616

AN:

4384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

412

824

1237

1649

2061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.137

AC:

20781

AN:

152146

Hom.:

1845

Cov.:

AF XY:

0.135

AC XY:

10072

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0496

AC:

2060

AN:

41512

American (AMR)

AF:

0.274

AC:

4184

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

707

AN:

3470

East Asian (EAS)

AF:

0.00231

AC:

AN:

5184

South Asian (SAS)

AF:

0.0647

AC:

312

AN:

4820

European-Finnish (FIN)

AF:

0.134

AC:

1421

AN:

10580

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11685

AN:

68004

Other (OTH)

AF:

0.146

AC:

308

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

907

1814

2722

3629

4536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.172

Hom.:

3422

Bravo

AF:

0.145

Asia WGS

AF:

0.0440

AC:

155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.5

(source)

DANN

Benign

0.60

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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