18-72542514-C-A

Position:

• chr18-72542514-C-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.-166-188G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 151,942 control chromosomes in the GnomAD database, including 883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.051 (883 hom., cov: 31)
• Consequence: CBLN2 NM_182511.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.683

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=-0.58).
• BP6: Variant 18-72542514-C-A is Benign according to our data. Variant chr18-72542514-C-A is described in ClinVar as [Benign]. Clinvar id is 1261360.Status of the report is criteria_provided_single_submitter, 1 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.-166-188G>T		intron_variant		ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9	c.-166-188G>T		intron_variant		1	NM_182511.4	P1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7705 AN: 151820 Hom.: 880 Cov.: 31

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0280

Gnomad OTH AF: 0.0503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0508 AC: 7713 AN: 151942 Hom.: 883 Cov.: 31 AF XY: 0.0577 AC XY: 4285 AN XY: 74236

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.0920

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0280

Gnomad4 OTH AF: 0.0512

Alfa AF: 0.0340 Hom.: 33

Bravo AF: 0.0478

Asia WGS AF: 0.238 AC: 826 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.93

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: rs77501815; hg19: chr18-70209749;