Genetic Variant NM_001159773.2: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

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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