18-72541663-G-T

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.357+141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 615,226 control chromosomes in the GnomAD database, including 231,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (46941 hom., cov: 33)
  • Exomes 𝑓: 0.88 (184334 hom.)
• Consequence: CBLN2 NM_182511.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

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=-0.84).
• BP6: Variant 18-72541663-G-T is Benign according to our data. Variant chr18-72541663-G-T is described in ClinVar as [Benign]. Clinvar id is 1277122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4	c.357+141C>A		intron_variant		ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9	c.357+141C>A		intron_variant		1	NM_182511.4	P1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111682 AN: 151994 Hom.: 46930 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.877 AC: 406211 AN: 463112 Hom.: 184334 AF XY: 0.875 AC XY: 208610 AN XY: 238542

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.965

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.898

Gnomad4 NFE exome AF: 0.948

Gnomad4 OTH exome AF: 0.856

GnomAD4 genome AF: 0.734 AC: 111721 AN: 152114 Hom.: 46941 Cov.: 33 AF XY: 0.731 AC XY: 54362 AN XY: 74348

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.964

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.786

Alfa AF: 0.860 Hom.: 8196

Bravo AF: 0.714

Asia WGS AF: 0.564 AC: 1962 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 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.94
Dann	Benign	0.47

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: rs1223504; hg19: chr18-70208898;