rs59751882

Variant names:

• chr18-72538166-G-A
• rs59751882
• NM_182511.4:c.*10C>T

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.*10C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,613,870 control chromosomes in the GnomAD database, including 5,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (673 hom., cov: 32)
  • Exomes 𝑓: 0.022 (4684 hom.)
• Consequence: CBLN2 NM_182511.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.867
• Publications: 5 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=-0.82).
• BP6: Variant 18-72538166-G-A is Benign according to our data. Variant chr18-72538166-G-A is described in ClinVar as Benign. ClinVar VariationId is 1284185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 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.*10C>T		3_prime_UTR	Exon 5 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.*10C>T		3_prime_UTR	Exon 5 of 5	ENSP00000269503.4	Q8IUK8
	CBLN2	ENST00000585159.5	TSL:1	c.*10C>T		3_prime_UTR	Exon 4 of 4	ENSP00000463771.1	Q8IUK8
	CBLN2	ENST00000881350.1		c.*10C>T		3_prime_UTR	Exon 3 of 3	ENSP00000551409.1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4738 AN: 151950 Hom.: 672 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00407

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0535 AC: 13442 AN: 251394 AF XY: 0.0500

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.0366

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.0594

Gnomad NFE exome AF: 0.00373

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0221 AC: 32331 AN: 1461802 Hom.: 4684 Cov.: 31 AF XY: 0.0220 AC XY: 16007 AN XY: 727202

African (AFR) AF: 0.00893 AC: 299 AN: 33478

American (AMR) AF: 0.0347 AC: 1552 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00302 AC: 79 AN: 26132

East Asian (EAS) AF: 0.462 AC: 18322 AN: 39686

South Asian (SAS) AF: 0.0310 AC: 2674 AN: 86256

European-Finnish (FIN) AF: 0.0577 AC: 3081 AN: 53418

Middle Eastern (MID) AF: 0.00590 AC: 34 AN: 5764

European-Non Finnish (NFE) AF: 0.00380 AC: 4228 AN: 1111956

Other (OTH) AF: 0.0341 AC: 2062 AN: 60392

GnomAD4 genome AF: 0.0312 AC: 4746 AN: 152068 Hom.: 673 Cov.: 32 AF XY: 0.0367 AC XY: 2725 AN XY: 74318

African (AFR) AF: 0.0113 AC: 469 AN: 41504

American (AMR) AF: 0.0352 AC: 538 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3466

East Asian (EAS) AF: 0.484 AC: 2478 AN: 5118

South Asian (SAS) AF: 0.0455 AC: 219 AN: 4812

European-Finnish (FIN) AF: 0.0650 AC: 688 AN: 10582

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00407 AC: 277 AN: 67976

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0203 Hom.: 320

Bravo AF: 0.0310

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.82
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.87
Mutation Taster		=100/0	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: rs59751882; hg19: chr18-70205401; COSMIC: COSV54050670;