rs8093502

Positions:

• chr18-72618222-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000581073.1(CBLN2):​c.15+20103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 227,010 control chromosomes in the GnomAD database, including 2,963 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1845 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1118 hom.)
• Consequence: CBLN2 ENST00000581073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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]

HNRNPA1P11 (HGNC:39129): (heterogeneous nuclear ribonucleoprotein A1 pseudogene 11)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	XM_006722394.4	c.-910+20103G>A		intron_variant
CBLN2	XM_011525824.3	c.-913+20103G>A		intron_variant
CBLN2	XM_017025559.2	c.-1414+20103G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000581073.1	c.15+20103G>A		intron_variant		4
CBLN2	ENST00000580889.1	n.104+20130G>A		intron_variant, non_coding_transcript_variant		3
HNRNPA1P11	ENST00000580106.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20778 AN: 152028 Hom.: 1844 Cov.: 32

Gnomad AFR AF: 0.0498

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0647

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.146 AC: 10953 AN: 74864 Hom.: 1118 Cov.: 0 AF XY: 0.143 AC XY: 5690 AN XY: 39660

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.00129

Gnomad4 SAS exome AF: 0.0715

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.137 AC: 20781 AN: 152146 Hom.: 1845 Cov.: 32 AF XY: 0.135 AC XY: 10072 AN XY: 74368

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.146

Alfa AF: 0.176 Hom.: 2714

Bravo AF: 0.145

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.5
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8093502; hg19: chr18-70285457;