18-72542245-T-C

Variant names:

• chr18-72542245-T-C
• rs8094389
• NM_182511.4:c.-85A>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.-85A>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 0.0513 in 930,030 control chromosomes in the GnomAD database, including 3,833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (1474 hom., cov: 32)
  • Exomes 𝑓: 0.043 (2359 hom.)
• Consequence: CBLN2 NM_182511.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04
• 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=-0.84).
• BP6: Variant 18-72542245-T-C is Benign according to our data. Variant chr18-72542245-T-C is described in ClinVar as Benign. ClinVar VariationId is 1247859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 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.-85A>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.-85A>G		5_prime_UTR	Exon 3 of 5	ENSP00000269503.4	Q8IUK8
	CBLN2	ENST00000585159.5	TSL:1	c.-85A>G		5_prime_UTR	Exon 2 of 4	ENSP00000463771.1	Q8IUK8
	CBLN2	ENST00000881350.1		c.-85A>G		5_prime_UTR	Exon 1 of 3	ENSP00000551409.1

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14382 AN: 151464 Hom.: 1465 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.0924

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0810

GnomAD4 exome AF: 0.0428 AC: 33307 AN: 778458 Hom.: 2359 Cov.: 10 AF XY: 0.0418 AC XY: 15534 AN XY: 371798

African (AFR) AF: 0.172 AC: 2649 AN: 15406

American (AMR) AF: 0.0463 AC: 264 AN: 5706

Ashkenazi Jewish (ASJ) AF: 0.0218 AC: 210 AN: 9614

East Asian (EAS) AF: 0.464 AC: 6522 AN: 14064

South Asian (SAS) AF: 0.0732 AC: 1006 AN: 13740

European-Finnish (FIN) AF: 0.0868 AC: 1503 AN: 17312

Middle Eastern (MID) AF: 0.0417 AC: 86 AN: 2064

European-Non Finnish (NFE) AF: 0.0285 AC: 19095 AN: 669944

Other (OTH) AF: 0.0644 AC: 1972 AN: 30608

GnomAD4 genome AF: 0.0951 AC: 14419 AN: 151572 Hom.: 1474 Cov.: 32 AF XY: 0.101 AC XY: 7458 AN XY: 74094

African (AFR) AF: 0.165 AC: 6822 AN: 41342

American (AMR) AF: 0.0613 AC: 935 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2724 AN: 5054

South Asian (SAS) AF: 0.0927 AC: 446 AN: 4810

European-Finnish (FIN) AF: 0.105 AC: 1103 AN: 10486

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

European-Non Finnish (NFE) AF: 0.0302 AC: 2052 AN: 67848

Other (OTH) AF: 0.0844 AC: 178 AN: 2108

Alfa AF: 0.0540 Hom.: 84

Bravo AF: 0.0981

Asia WGS AF: 0.264 AC: 915 AN: 3474

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	-0.84
CADD	Benign	11
DANN	Benign	0.53
PhyloP100		-1.0
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: rs8094389; hg19: chr18-70209480;