18-72542403-C-T

Position:

• chr18-72542403-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.693

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4	c.-166-77G>A		intron_variant		ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9	c.-166-77G>A		intron_variant		1	NM_182511.4	P1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7879 AN: 151956 Hom.: 885 Cov.: 31

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

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.0312

Gnomad4 ASJ exome AF: 0.0140

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.0554

Gnomad4 FIN exome AF: 0.0751

Gnomad4 NFE exome AF: 0.0211

Gnomad4 OTH exome AF: 0.0477

GnomAD4 genome AF: 0.0519 AC: 7885 AN: 152072 Hom.: 887 Cov.: 31 AF XY: 0.0587 AC XY: 4363 AN XY: 74318

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0452

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.0898

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0350 Hom.: 35

Bravo AF: 0.0488

Asia WGS AF: 0.236 AC: 817 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.78
CADD	Benign	4.9
DANN	Benign	0.75

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: rs72634431; hg19: chr18-70209638;