18-72542461-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_182511.4(CBLN2):c.-166-135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 184,812 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (14 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (1 hom.)
• Consequence: CBLN2 NM_182511.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.671

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=-0.87).
• BP6: Variant 18-72542461-G-T is Benign according to our data. Variant chr18-72542461-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00832 (1265/151966) while in subpopulation SAS AF= 0.0394 (189/4800). AF 95% confidence interval is 0.0348. There are 14 homozygotes in gnomad4. There are 647 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	NM_182511.4	c.-166-135C>A		intron_variant		ENST00000269503.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000269503.9	c.-166-135C>A		intron_variant		1	NM_182511.4	P1

Frequencies

GnomAD3 genomes AF: 0.00832 AC: 1264 AN: 151848 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.00247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00977

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.00652 AC: 214 AN: 32846 Hom.: 1 AF XY: 0.00616 AC XY: 107 AN XY: 17358

Gnomad4 AFR exome AF: 0.00391

Gnomad4 AMR exome AF: 0.00629

Gnomad4 ASJ exome AF: 0.00523

Gnomad4 EAS exome AF: 0.0172

Gnomad4 SAS exome AF: 0.0317

Gnomad4 FIN exome AF: 0.000303

Gnomad4 NFE exome AF: 0.00693

Gnomad4 OTH exome AF: 0.00486

GnomAD4 genome AF: 0.00832 AC: 1265 AN: 151966 Hom.: 14 Cov.: 31 AF XY: 0.00871 AC XY: 647 AN XY: 74282

Gnomad4 AFR AF: 0.00246

Gnomad4 AMR AF: 0.00916

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00977

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00907 Hom.: 1

Bravo AF: 0.00745

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 30, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.1
Dann	Benign	0.83

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: rs76871698; hg19: chr18-70209696;