dbSNP rs2377301: CANT1:c.-146-324G>A (chr17-78998287-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_001159773.2(CANT1):c.-146-324G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 157,274 control chromosomes in the GnomAD database, including 1,761 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 0.13 ( 1709 hom., cov: 33)

Exomes 𝑓: 0.14 ( 52 hom. )

Consequence

CANT1
NM_001159773.2 intron

Scores

Splicing: ADA: 0.0001073

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.346

Publications

14 publications found

Variant links:

Genes affected

CANT1 (HGNC:19721): (calcium activated nucleotidase 1) This protein encoded by this gene belongs to the apyrase family. It functions as a calcium-dependent nucleotidase with a preference for UDP. Mutations in this gene are associated with Desbuquois dysplasia with hand anomalies. Alternatively spliced transcript variants have been noted for this gene.[provided by RefSeq, Mar 2010]

CANT1 Gene-Disease associations (from GenCC):

Desbuquois dysplasia 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Desbuquois dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CANT1 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CANT1	NM_001159773.2 link	c.-146-324G>A	intron_variant	Intron 1 of 4	ENST00000392446.10	NP_001153245.1	Q8WVQ1-1A0A024R8U8
CANT1	NM_001159772.2 link	c.-285-1G>A	splice_acceptor_variant, intron_variant	Intron 1 of 5		NP_001153244.1	Q8WVQ1-1A0A024R8U8
CANT1	NM_138793.4 link	c.-341-324G>A	intron_variant	Intron 1 of 3		NP_620148.1	Q8WVQ1-1A0A024R8U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CANT1	ENST00000392446.10 link	c.-146-324G>A		intron_variant	Intron 1 of 4	1	NM_001159773.2	ENSP00000376241.4		Q8WVQ1-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20019

AN:

152158

Hom.:

1700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0949

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.0766

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.0931

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.138

AC:

690

AN:

4998

Hom.:

Cov.:

AF XY:

0.135

AC XY:

326

AN XY:

2422

show subpopulations

African (AFR)

AF:

0.0493

AC:

AN:

142

American (AMR)

AF:

0.293

AC:

AN:

140

Ashkenazi Jewish (ASJ)

AF:

0.0678

AC:

AN:

354

East Asian (EAS)

AF:

0.253

AC:

240

AN:

950

South Asian (SAS)

AF:

0.143

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.0294

AC:

AN:

European-Non Finnish (NFE)

AF:

0.109

AC:

317

AN:

2906

Other (OTH)

AF:

0.125

AC:

AN:

440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.132

AC:

20030

AN:

152276

Hom.:

1709

Cov.:

AF XY:

0.136

AC XY:

10142

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0947

AC:

3935

AN:

41560

American (AMR)

AF:

0.253

AC:

3874

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0766

AC:

266

AN:

3472

East Asian (EAS)

AF:

0.302

AC:

1565

AN:

5182

South Asian (SAS)

AF:

0.236

AC:

1139

AN:

4830

European-Finnish (FIN)

AF:

0.0931

AC:

988

AN:

10614

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7775

AN:

68012

Other (OTH)

AF:

0.129

AC:

272

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

890

1779

2669

3558

4448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.126

Hom.:

913

Bravo

AF:

0.141

Asia WGS

AF:

0.266

AC:

925

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.3

(source)

DANN

Benign

0.85

PhyloP100

0.35

PromoterAI

0.059

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0060

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