18-72542275-G-C

Position:

• chr18-72542275-G-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.-115C>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 0.0569 in 577,664 control chromosomes in the GnomAD database, including 2,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (1492 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1398 hom.)
• Consequence: CBLN2 NM_182511.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.58

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=-0.98).
• BP6: Variant 18-72542275-G-C is Benign according to our data. Variant chr18-72542275-G-C is described in ClinVar as [Benign]. Clinvar id is 1282546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4	c.-115C>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.-115C>G		5_prime_UTR_variant	3/5	1	NM_182511.4	P1

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14487 AN: 151862 Hom.: 1483 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0805

GnomAD4 exome AF: 0.0430 AC: 18321 AN: 425692 Hom.: 1398 Cov.: 7 AF XY: 0.0421 AC XY: 8784 AN XY: 208518

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0448

Gnomad4 ASJ exome AF: 0.0197

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.0693

Gnomad4 FIN exome AF: 0.0819

Gnomad4 NFE exome AF: 0.0264

Gnomad4 OTH exome AF: 0.0618

GnomAD4 genome AF: 0.0956 AC: 14524 AN: 151972 Hom.: 1492 Cov.: 32 AF XY: 0.101 AC XY: 7508 AN XY: 74268

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.0926

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.0597 Hom.: 83

Bravo AF: 0.0986

Asia WGS AF: 0.264 AC: 916 AN: 3476

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	-0.98
CADD	Benign	0.060
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: rs8093595; hg19: chr18-70209510;