rs8093595

Variant names:

• chr18-72542275-G-A
• rs8093595
• NM_182511.4:c.-115C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-72542275-G-A
• chr18-72542275-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182511.4(CBLN2):​c.-115C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000234 in 427,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CBLN2 NM_182511.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182511.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLN2	NM_182511.4	MANE Select	c.-115C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	NP_872317.1	Q8IUK8
	CBLN2	NM_182511.4	MANE Select	c.-115C>T		5_prime_UTR	Exon 3 of 5	NP_872317.1	Q8IUK8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLN2	ENST00000269503.9	TSL:1 MANE Select	c.-115C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	ENSP00000269503.4	Q8IUK8
	CBLN2	ENST00000585159.5	TSL:1	c.-115C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000463771.1	Q8IUK8
	CBLN2	ENST00000269503.9	TSL:1 MANE Select	c.-115C>T		5_prime_UTR	Exon 3 of 5	ENSP00000269503.4	Q8IUK8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000234 AC: 1 AN: 427012 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 209194

African (AFR) AF: 0.00 AC: 0 AN: 8334

American (AMR) AF: 0.00 AC: 0 AN: 4782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6910

East Asian (EAS) AF: 0.00 AC: 0 AN: 10664

South Asian (SAS) AF: 0.00 AC: 0 AN: 6754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1396

European-Non Finnish (NFE) AF: 0.00000283 AC: 1 AN: 353904

Other (OTH) AF: 0.00 AC: 0 AN: 18578

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.090
DANN	Benign	0.97
PhyloP100		-3.6

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

Other links and lift over

dbSNP: rs8093595; hg19: chr18-70209510;