17-78992703-G-A

Position:

• chr17-78992703-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.585

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]

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	HGVSp	Effect	#exon/exons	MANE	UniProt
CANT1	NM_001159773.2	c.*847C>T		3_prime_UTR_variant	5/5	ENST00000392446.10
CANT1	NM_001159772.2	c.*847C>T		3_prime_UTR_variant	6/6
CANT1	NM_138793.4	c.*847C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CANT1	ENST00000392446.10	c.*847C>T		3_prime_UTR_variant	5/5	1	NM_001159773.2	P1
CANT1	ENST00000302345.6	c.*847C>T		3_prime_UTR_variant	4/4	2		P1
CANT1	ENST00000620915.4	c.*847C>T		3_prime_UTR_variant	4/4	5		P1
CANT1	ENST00000592228.1	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.: 32

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

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.: 0 AF XY: 0.108 AC XY: 26611 AN XY: 245368

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.: 32 AF XY: 0.125 AC XY: 9325 AN XY: 74374

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:2

Revision: criteria provided, multiple submitters, no conflicts

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Other links and lift over

dbSNP: rs11891; hg19: chr17-76988785; COSMIC: COSV56605178; COSMIC: COSV56605178;