Genetic Variant CBLN2:c.357+141C>A (chr18-72541663-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_182511.4(CBLN2):c.357+141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 615,226 control chromosomes in the GnomAD database, including 231,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.73 ( 46941 hom., cov: 33)

Exomes 𝑓: 0.88 ( 184334 hom. )

Consequence

CBLN2
NM_182511.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

Publications

2 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 18-72541663-G-T is Benign according to our data. Variant chr18-72541663-G-T is described in ClinVar as Benign. ClinVar VariationId is 1277122.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 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.357+141C>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.357+141C>A	intron	N/A	ENSP00000269503.4	Q8IUK8
CBLN2	ENST00000585159.5	TSL:1	c.357+141C>A	intron	N/A	ENSP00000463771.1	Q8IUK8
CBLN2	ENST00000881350.1		c.357+141C>A	intron	N/A	ENSP00000551409.1

Frequencies

GnomAD3 genomes

AF:

0.735

AC:

111682

AN:

151994

Hom.:

46930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.936

Gnomad AMR

AF:

0.853

Gnomad ASJ

AF:

0.964

Gnomad EAS

AF:

0.376

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.947

Gnomad OTH

AF:

0.788

GnomAD4 exome

AF:

0.877

AC:

406211

AN:

463112

Hom.:

184334

AF XY:

0.875

AC XY:

208610

AN XY:

238542

show subpopulations

African (AFR)

AF:

0.314

AC:

3443

AN:

10952

American (AMR)

AF:

0.879

AC:

11818

AN:

13442

Ashkenazi Jewish (ASJ)

AF:

0.965

AC:

12095

AN:

12530

East Asian (EAS)

AF:

0.407

AC:

10626

AN:

26088

South Asian (SAS)

AF:

0.746

AC:

26400

AN:

35388

European-Finnish (FIN)

AF:

0.898

AC:

25263

AN:

28134

Middle Eastern (MID)

AF:

0.903

AC:

1799

AN:

1992

European-Non Finnish (NFE)

AF:

0.948

AC:

293054

AN:

309224

Other (OTH)

AF:

0.856

AC:

21713

AN:

25362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1912

3824

5735

7647

9559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2612

5224

7836

10448

13060

<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:

0.734

AC:

111721

AN:

152114

Hom.:

46941

Cov.:

AF XY:

0.731

AC XY:

54362

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.323

AC:

13388

AN:

41508

American (AMR)

AF:

0.853

AC:

13054

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.964

AC:

3347

AN:

3472

East Asian (EAS)

AF:

0.375

AC:

1923

AN:

5130

South Asian (SAS)

AF:

0.713

AC:

3436

AN:

4822

European-Finnish (FIN)

AF:

0.891

AC:

9441

AN:

10596

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.947

AC:

64355

AN:

67974

Other (OTH)

AF:

0.786

AC:

1659

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

892

1784

2677

3569

4461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.860

Hom.:

8196

Bravo

AF:

0.714

Asia WGS

AF:

0.564

AC:

1962

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.94

(source)

DANN

Benign

0.47

PhyloP100

1.6

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