17-78992703-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001159773.2(CANT1):c.*847C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 595,574 control chromosomes in the GnomAD database, including 4,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1444 hom., cov: 32)

Exomes 𝑓: 0.11 ( 3366 hom. )

Consequence

CANT1
NM_001159773.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.585

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-78992703-G-A is Benign according to our data. Variant chr17-78992703-G-A is described in ClinVar as [Benign]. Clinvar id is 325681.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78992703-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
CANT1	NM_001159773.2 linkuse as main transcript	c.*847C>T	3_prime_UTR_variant	5/5	ENST00000392446.10
CANT1	NM_001159772.2 linkuse as main transcript	c.*847C>T	3_prime_UTR_variant	6/6
CANT1	NM_138793.4 linkuse as main transcript	c.*847C>T	3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CANT1	ENST00000392446.10 linkuse as main transcript	c.*847C>T		3_prime_UTR_variant	5/5	1	NM_001159773.2	P1	Q8WVQ1-1
CANT1	ENST00000302345.6 linkuse as main transcript	c.*847C>T		3_prime_UTR_variant	4/4	2		P1	Q8WVQ1-1
CANT1	ENST00000620915.4 linkuse as main transcript	c.*847C>T		3_prime_UTR_variant	4/4	5		P1	Q8WVQ1-1
CANT1	ENST00000592228.1 linkuse as main transcript	c.706C>T	p.Arg236Cys	missense_variant, NMD_transcript_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18968

AN:

151994

Hom.:

1430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0758

Gnomad ASJ

AF:

0.0865

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0885

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.113

AC:

25909

AN:

228632

Hom.:

2058

AF XY:

0.112

AC XY:

14144

AN XY:

126404

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.0595

Gnomad ASJ exome

AF:

0.0847

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0870

Gnomad OTH exome

AF:

0.0897

GnomAD4 exome

AF:

0.108

AC:

47888

AN:

443462

Hom.:

3366

Cov.:

AF XY:

0.108

AC XY:

26611

AN XY:

245368

show subpopulations

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.0604

Gnomad4 ASJ exome

AF:

0.0853

Gnomad4 EAS exome

AF:

0.309

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0882

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.125

AC:

19018

AN:

152112

Hom.:

1444

Cov.:

AF XY:

0.125

AC XY:

9325

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0758

Gnomad4 ASJ

AF:

0.0865

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.0885

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.0951

Hom.:

1673

Bravo

AF:

0.129

Asia WGS

AF:

0.231

AC:

800

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Desbuquois dysplasia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

3.6

Dann

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over