18-72542245-T-C

Position:

• chr18-72542245-T-C

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.-85A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 930,030 control chromosomes in the GnomAD database, including 3,833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (1474 hom., cov: 32)
  • Exomes 𝑓: 0.043 (2359 hom.)
• Consequence: CBLN2 NM_182511.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04

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=-0.84).
• BP6: Variant 18-72542245-T-C is Benign according to our data. Variant chr18-72542245-T-C is described in ClinVar as [Benign]. Clinvar id is 1247859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4	c.-85A>G		5_prime_UTR_variant	3/5	ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9	c.-85A>G		5_prime_UTR_variant	3/5	1	NM_182511.4	P1

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14382 AN: 151464 Hom.: 1465 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.0924

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0810

GnomAD4 exome AF: 0.0428 AC: 33307 AN: 778458 Hom.: 2359 Cov.: 10 AF XY: 0.0418 AC XY: 15534 AN XY: 371798

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.0463

Gnomad4 ASJ exome AF: 0.0218

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.0732

Gnomad4 FIN exome AF: 0.0868

Gnomad4 NFE exome AF: 0.0285

Gnomad4 OTH exome AF: 0.0644

GnomAD4 genome AF: 0.0951 AC: 14419 AN: 151572 Hom.: 1474 Cov.: 32 AF XY: 0.101 AC XY: 7458 AN XY: 74094

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0844

Alfa AF: 0.0540 Hom.: 84

Bravo AF: 0.0981

Asia WGS AF: 0.264 AC: 915 AN: 3474

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	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.53

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: rs8094389; hg19: chr18-70209480;