18-72542275-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182511.4(CBLN2):​c.-115C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 577,664 control chromosomes in the GnomAD database, including 2,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (1492 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1398 hom.)
• Consequence: CBLN2 NM_182511.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.58
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 18-72542275-G-C is Benign according to our data. Variant chr18-72542275-G-C is described in ClinVar as Benign. ClinVar VariationId is 1282546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

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>G		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>G		5_prime_UTR	Exon 3 of 5	ENSP00000269503.4	Q8IUK8
	CBLN2	ENST00000585159.5	TSL:1	c.-115C>G		5_prime_UTR	Exon 2 of 4	ENSP00000463771.1	Q8IUK8
	CBLN2	ENST00000881350.1		c.-115C>G		5_prime_UTR	Exon 1 of 3	ENSP00000551409.1

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14487 AN: 151862 Hom.: 1483 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0805

GnomAD4 exome AF: 0.0430 AC: 18321 AN: 425692 Hom.: 1398 Cov.: 7 AF XY: 0.0421 AC XY: 8784 AN XY: 208518

African (AFR) AF: 0.159 AC: 1318 AN: 8284

American (AMR) AF: 0.0448 AC: 213 AN: 4754

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 136 AN: 6898

East Asian (EAS) AF: 0.432 AC: 4402 AN: 10180

South Asian (SAS) AF: 0.0693 AC: 467 AN: 6738

European-Finnish (FIN) AF: 0.0819 AC: 1275 AN: 15562

Middle Eastern (MID) AF: 0.0380 AC: 53 AN: 1394

European-Non Finnish (NFE) AF: 0.0264 AC: 9314 AN: 353386

Other (OTH) AF: 0.0618 AC: 1143 AN: 18496

GnomAD4 genome AF: 0.0956 AC: 14524 AN: 151972 Hom.: 1492 Cov.: 32 AF XY: 0.101 AC XY: 7508 AN XY: 74268

African (AFR) AF: 0.166 AC: 6895 AN: 41482

American (AMR) AF: 0.0615 AC: 940 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3472

East Asian (EAS) AF: 0.538 AC: 2736 AN: 5086

South Asian (SAS) AF: 0.0926 AC: 447 AN: 4826

European-Finnish (FIN) AF: 0.106 AC: 1117 AN: 10562

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0302 AC: 2053 AN: 67946

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

Alfa AF: 0.0597 Hom.: 83

Bravo AF: 0.0986

Asia WGS AF: 0.264 AC: 916 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.060
DANN	Benign	0.75
PhyloP100		-3.6
Mutation Taster		=300/0	polymorphism (auto)

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;