dbSNP rs7734102: 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:

Genome browser will be placed here

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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