ENST00000581073.1:c.16-21014A>G

Variant names:

• chr18-72559786-T-C
• rs17086172
• ENST00000581073.1:c.16-21014A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CBLN2	XM_006722394.4	c.-909-7150A>G		intron_variant	Intron 1 of 6		XP_006722457.1
CBLN2	XM_011525824.3	c.-912-7150A>G		intron_variant	Intron 1 of 6		XP_011524126.1
CBLN2	XM_017025559.2	c.-1413-7150A>G		intron_variant	Intron 1 of 6		XP_016881048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLN2	ENST00000581073.1	c.16-21014A>G		intron_variant	Intron 1 of 2	4		ENSP00000462632.1
CBLN2	ENST00000580889.1	n.105-7150A>G		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.0616 AC: 2561 AN: 41562

American (AMR) AF: 0.0484 AC: 741 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3468

East Asian (EAS) AF: 0.0950 AC: 491 AN: 5166

South Asian (SAS) AF: 0.0551 AC: 266 AN: 4826

European-Finnish (FIN) AF: 0.0849 AC: 899 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0649 AC: 4412 AN: 68026

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0645 Hom.: 605

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
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17086172; hg19: chr18-70227021;