18-72542657-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182511.4(CBLN2):c.-166-331C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,106 control chromosomes in the GnomAD database, including 896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.051 (896 hom., cov: 31)
• Consequence: CBLN2 NM_182511.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.528

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-72542657-G-A is Benign according to our data. Variant chr18-72542657-G-A is described in ClinVar as [Benign]. Clinvar id is 1268943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4	c.-166-331C>T		intron_variant		ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9	c.-166-331C>T		intron_variant		1	NM_182511.4	P1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7753 AN: 151988 Hom.: 894 Cov.: 31

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0510 AC: 7759 AN: 152106 Hom.: 896 Cov.: 31 AF XY: 0.0581 AC XY: 4321 AN XY: 74344

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0437

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.0901

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0207 Hom.: 10

Bravo AF: 0.0478

Asia WGS AF: 0.236 AC: 821 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.88
Cadd	Benign	4.8
Dann	Benign	0.92

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

Other links and lift over

dbSNP: rs67792236; hg19: chr18-70209892;