Genetic Variant CANX:c.1725+37C>T (chr5-179726796-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001746.4(CANX):c.1725+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,428,100 control chromosomes in the GnomAD database, including 74,059 homozygotes. 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: 𝑓 0.28 ( 6302 hom., cov: 32)

Exomes 𝑓: 0.32 ( 67757 hom. )

Consequence

CANX
NM_001746.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.185

Publications

10 publications found

Variant links:

Genes affected

CANX (HGNC:1473): (calnexin) This gene encodes a member of the calnexin family of molecular chaperones. The encoded protein is a calcium-binding, endoplasmic reticulum (ER)-associated protein that interacts transiently with newly synthesized N-linked glycoproteins, facilitating protein folding and assembly. It may also play a central role in the quality control of protein folding by retaining incorrectly folded protein subunits within the ER for degradation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2018]

CANX links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CANX	NM_001746.4 link	c.1725+37C>T		intron_variant	Intron 14 of 14	ENST00000247461.9	NP_001737.1	P27824-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CANX	ENST00000247461.9 link	c.1725+37C>T		intron_variant	Intron 14 of 14	1	NM_001746.4	ENSP00000247461.4		P27824-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42545

AN:

151824

Hom.:

6296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.285

GnomAD2 exomes

AF:

0.273

AC:

67740

AN:

247854

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.320

AC:

408351

AN:

1276158

Hom.:

67757

Cov.:

AF XY:

0.315

AC XY:

203338

AN XY:

644514

show subpopulations

African (AFR)

AF:

0.216

AC:

6372

AN:

29478

American (AMR)

AF:

0.201

AC:

8662

AN:

43108

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

6741

AN:

24740

East Asian (EAS)

AF:

0.165

AC:

6423

AN:

38854

South Asian (SAS)

AF:

0.191

AC:

15669

AN:

82152

European-Finnish (FIN)

AF:

0.349

AC:

18596

AN:

53274

Middle Eastern (MID)

AF:

0.258

AC:

1400

AN:

5436

European-Non Finnish (NFE)

AF:

0.347

AC:

327915

AN:

945042

Other (OTH)

AF:

0.306

AC:

16573

AN:

54074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12976

25952

38929

51905

64881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9738

19476

29214

38952

48690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.280

AC:

42581

AN:

151942

Hom.:

6302

Cov.:

AF XY:

0.277

AC XY:

20553

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.216

AC:

8960

AN:

41430

American (AMR)

AF:

0.220

AC:

3360

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

921

AN:

3468

East Asian (EAS)

AF:

0.170

AC:

877

AN:

5168

South Asian (SAS)

AF:

0.190

AC:

918

AN:

4820

European-Finnish (FIN)

AF:

0.346

AC:

3647

AN:

10540

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22977

AN:

67936

Other (OTH)

AF:

0.282

AC:

596

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1535

3070

4605

6140

7675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.310

Hom.:

13008

Bravo

AF:

0.267

Asia WGS

AF:

0.180

AC:

624

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.50

(source)

DANN

Benign

0.24

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over