17-78992457-G-A

Position:

• chr17-78992457-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001159773.2(CANT1):​c.*1093C>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 0.00495 in 368,382 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (3 hom.)
• Consequence: CANT1 NM_001159773.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.874

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=-0.88).
• BP6: Variant 17-78992457-G-A is Benign according to our data. Variant chr17-78992457-G-A is described in ClinVar as [Benign]. Clinvar id is 325674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00736 (1120/152238) while in subpopulation AFR AF= 0.019 (788/41538). AF 95% confidence interval is 0.0179. There are 5 homozygotes in gnomad4. There are 537 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CANT1	NM_001159773.2	c.*1093C>T		3_prime_UTR_variant	5/5	ENST00000392446.10
CANT1	NM_001159772.2	c.*1093C>T		3_prime_UTR_variant	6/6
CANT1	NM_138793.4	c.*1093C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CANT1	ENST00000392446.10	c.*1093C>T		3_prime_UTR_variant	5/5	1	NM_001159773.2	P1
CANT1	ENST00000302345.6	c.*1093C>T		3_prime_UTR_variant	4/4	2		P1
CANT1	ENST00000620915.4	c.*1093C>T		3_prime_UTR_variant	4/4	5		P1
CANT1	ENST00000592228.1	c.*157C>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	5

Frequencies

GnomAD3 genomes AF: 0.00736 AC: 1120 AN: 152120 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00326 AC: 704 AN: 216144 Hom.: 3 Cov.: 0 AF XY: 0.00283 AC XY: 316 AN XY: 111580

Gnomad4 AFR exome AF: 0.0203

Gnomad4 AMR exome AF: 0.00397

Gnomad4 ASJ exome AF: 0.00720

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.000168

Gnomad4 NFE exome AF: 0.00261

Gnomad4 OTH exome AF: 0.00396

GnomAD4 genome AF: 0.00736 AC: 1120 AN: 152238 Hom.: 5 Cov.: 32 AF XY: 0.00722 AC XY: 537 AN XY: 74428

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00474 Hom.: 0

Bravo AF: 0.00872

Asia WGS AF: 0.00144 AC: 6 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 12, 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	-0.88
CADD	Benign	4.9
DANN	Benign	0.76

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: rs8078860; hg19: chr17-76988539;