Variant 18-72542461-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182511.4(CBLN2):c.-166-135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 184,812 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 14 hom., cov: 31)

Exomes 𝑓: 0.0065 ( 1 hom. )

Consequence

CBLN2
NM_182511.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.671

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 18-72542461-G-T is Benign according to our data. Variant chr18-72542461-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00832 (1265/151966) while in subpopulation SAS AF= 0.0394 (189/4800). AF 95% confidence interval is 0.0348. There are 14 homozygotes in gnomad4. There are 647 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4 linkuse as main transcript	c.-166-135C>A		intron_variant		ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9 linkuse as main transcript	c.-166-135C>A		intron_variant		1	NM_182511.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00832

AC:

1264

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00917

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.0228

Gnomad SAS

AF:

0.0391

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00977

Gnomad OTH

AF:

0.00814

GnomAD4 exome

AF:

0.00652

AC:

214

AN:

32846

Hom.:

AF XY:

0.00616

AC XY:

107

AN XY:

17358

show subpopulations

Gnomad4 AFR exome

AF:

0.00391

Gnomad4 AMR exome

AF:

0.00629

Gnomad4 ASJ exome

AF:

0.00523

Gnomad4 EAS exome

AF:

0.0172

Gnomad4 SAS exome

AF:

0.0317

Gnomad4 FIN exome

AF:

0.000303

Gnomad4 NFE exome

AF:

0.00693

Gnomad4 OTH exome

AF:

0.00486

GnomAD4 genome

AF:

0.00832

AC:

1265

AN:

151966

Hom.:

Cov.:

AF XY:

0.00871

AC XY:

647

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00246

Gnomad4 AMR

AF:

0.00916

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.0233

Gnomad4 SAS

AF:

0.0394

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00977

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00907

Hom.:

Bravo

AF:

0.00745

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 30, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.1

DANN

Benign

0.83

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