chr18-72542086-C-A

Variant names:

• chr18-72542086-C-A
• rs7237888
• NM_182511.4:c.75G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_182511.4(CBLN2):​c.75G>T​(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 1,532,654 control chromosomes in the GnomAD database, including 613,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (45241 hom., cov: 32)
  • Exomes 𝑓: 0.90 (568402 hom.)
• Consequence: CBLN2 NM_182511.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.984
• Publications: 11 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 18-72542086-C-A is Benign according to our data. Variant chr18-72542086-C-A is described in ClinVar as Benign. ClinVar VariationId is 1250060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.984 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.931 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.75G>T	p.Pro25Pro	synonymous	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.75G>T	p.Pro25Pro	synonymous	Exon 3 of 5	ENSP00000269503.4	Q8IUK8
	CBLN2	ENST00000585159.5	TSL:1	c.75G>T	p.Pro25Pro	synonymous	Exon 2 of 4	ENSP00000463771.1	Q8IUK8
	CBLN2	ENST00000881350.1		c.75G>T	p.Pro25Pro	synonymous	Exon 1 of 3	ENSP00000551409.1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108509 AN: 151596 Hom.: 45233 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.758

GnomAD2 exomes AF: 0.853 AC: 134572 AN: 157814 AF XY: 0.855

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.901

Gnomad ASJ exome AF: 0.923

Gnomad EAS exome AF: 0.412

Gnomad FIN exome AF: 0.906

Gnomad NFE exome AF: 0.941

Gnomad OTH exome AF: 0.888

GnomAD4 exome AF: 0.897 AC: 1238976 AN: 1380948 Hom.: 568402 Cov.: 48 AF XY: 0.895 AC XY: 613236 AN XY: 685300

African (AFR) AF: 0.254 AC: 7177 AN: 28248

American (AMR) AF: 0.891 AC: 32306 AN: 36274

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 22301 AN: 24176

East Asian (EAS) AF: 0.413 AC: 13363 AN: 32348

South Asian (SAS) AF: 0.741 AC: 58179 AN: 78464

European-Finnish (FIN) AF: 0.898 AC: 32804 AN: 36512

Middle Eastern (MID) AF: 0.855 AC: 3415 AN: 3994

European-Non Finnish (NFE) AF: 0.942 AC: 1020938 AN: 1083770

Other (OTH) AF: 0.848 AC: 48493 AN: 57162

GnomAD4 genome AF: 0.715 AC: 108535 AN: 151706 Hom.: 45241 Cov.: 32 AF XY: 0.713 AC XY: 52838 AN XY: 74120

African (AFR) AF: 0.283 AC: 11721 AN: 41442

American (AMR) AF: 0.834 AC: 12722 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3194 AN: 3470

East Asian (EAS) AF: 0.377 AC: 1903 AN: 5054

South Asian (SAS) AF: 0.698 AC: 3364 AN: 4822

European-Finnish (FIN) AF: 0.891 AC: 9342 AN: 10488

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.937 AC: 63609 AN: 67860

Other (OTH) AF: 0.757 AC: 1597 AN: 2110

Alfa AF: 0.840 Hom.: 9697

Bravo AF: 0.692

Asia WGS AF: 0.552 AC: 1913 AN: 3464

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	-0.35
CADD	Benign	6.4
DANN	Benign	0.90
PhyloP100		-0.98
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: rs7237888; hg19: chr18-70209321; COSMIC: COSV54052416; COSMIC: COSV54052416;