18-72538166-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.*10C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,613,870 control chromosomes in the GnomAD database, including 5,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (673 hom., cov: 32)
  • Exomes 𝑓: 0.022 (4684 hom.)
• Consequence: CBLN2 NM_182511.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.867

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=-0.82).
• BP6: Variant 18-72538166-G-A is Benign according to our data. Variant chr18-72538166-G-A is described in ClinVar as [Benign]. Clinvar id is 1284185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4	c.*10C>T		3_prime_UTR_variant	5/5	ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9	c.*10C>T		3_prime_UTR_variant	5/5	1	NM_182511.4	P1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4738 AN: 151950 Hom.: 672 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00407

Gnomad OTH AF: 0.0292

GnomAD3 exomes AF: 0.0535 AC: 13442 AN: 251394 Hom.: 2415 AF XY: 0.0500 AC XY: 6796 AN XY: 135882

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.0366

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.498

Gnomad SAS exome AF: 0.0302

Gnomad FIN exome AF: 0.0594

Gnomad NFE exome AF: 0.00373

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0221 AC: 32331 AN: 1461802 Hom.: 4684 Cov.: 31 AF XY: 0.0220 AC XY: 16007 AN XY: 727202

Gnomad4 AFR exome AF: 0.00893

Gnomad4 AMR exome AF: 0.0347

Gnomad4 ASJ exome AF: 0.00302

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.0310

Gnomad4 FIN exome AF: 0.0577

Gnomad4 NFE exome AF: 0.00380

Gnomad4 OTH exome AF: 0.0341

GnomAD4 genome AF: 0.0312 AC: 4746 AN: 152068 Hom.: 673 Cov.: 32 AF XY: 0.0367 AC XY: 2725 AN XY: 74318

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0352

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.0455

Gnomad4 FIN AF: 0.0650

Gnomad4 NFE AF: 0.00407

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.00902 Hom.: 30

Bravo AF: 0.0310

Asia WGS AF: 0.197 AC: 683 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.74

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: rs59751882; hg19: chr18-70205401; COSMIC: COSV54050670;