rs17086172

Positions:

• chr18-72559786-T-C

Variant summary

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

The ENST00000581073.1(CBLN2):​c.16-21014A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,260 control chromosomes in the GnomAD database, including 302 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 0.063 (302 hom., cov: 33)
• Consequence: CBLN2 ENST00000581073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLN2	XM_006722394.4	c.-909-7150A>G		intron_variant
CBLN2	XM_011525824.3	c.-912-7150A>G		intron_variant
CBLN2	XM_017025559.2	c.-1413-7150A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLN2	ENST00000581073.1	c.16-21014A>G		intron_variant		4
CBLN2	ENST00000580889.1	n.105-7150A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9584 AN: 152142 Hom.: 301 Cov.: 33

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0630 AC: 9592 AN: 152260 Hom.: 302 Cov.: 33 AF XY: 0.0643 AC XY: 4788 AN XY: 74444

Gnomad4 AFR AF: 0.0616

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.0950

Gnomad4 SAS AF: 0.0551

Gnomad4 FIN AF: 0.0849

Gnomad4 NFE AF: 0.0649

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0617 Hom.: 76

Bravo AF: 0.0602

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17086172; hg19: chr18-70227021;