17-78992586-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001159773.2(CANT1):c.*964A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 460,682 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (110 hom., cov: 33)
  • Exomes 𝑓: 0.027 (121 hom.)
• Consequence: CANT1 NM_001159773.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.50

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-78992586-T-C is Benign according to our data. Variant chr17-78992586-T-C is described in ClinVar as [Benign]. Clinvar id is 325678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0328 (4990/152198) while in subpopulation AFR AF= 0.0451 (1873/41518). AF 95% confidence interval is 0.0434. There are 110 homozygotes in gnomad4. There are 2382 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 107 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CANT1	NM_001159773.2	c.*964A>G		3_prime_UTR_variant	5/5	ENST00000392446.10
CANT1	NM_001159772.2	c.*964A>G		3_prime_UTR_variant	6/6
CANT1	NM_138793.4	c.*964A>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CANT1	ENST00000392446.10	c.*964A>G		3_prime_UTR_variant	5/5	1	NM_001159773.2	P1
CANT1	ENST00000302345.6	c.*964A>G		3_prime_UTR_variant	4/4	2		P1
CANT1	ENST00000620915.4	c.*964A>G		3_prime_UTR_variant	4/4	5		P1
CANT1	ENST00000592228.1	c.*28A>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	5

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4984 AN: 152080 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0384

GnomAD3 exomes AF: 0.0236 AC: 2305 AN: 97510 Hom.: 20 AF XY: 0.0227 AC XY: 1167 AN XY: 51384

Gnomad AFR exome AF: 0.0403

Gnomad AMR exome AF: 0.0142

Gnomad ASJ exome AF: 0.0197

Gnomad EAS exome AF: 0.0245

Gnomad SAS exome AF: 0.0162

Gnomad FIN exome AF: 0.0191

Gnomad NFE exome AF: 0.0286

Gnomad OTH exome AF: 0.0243

GnomAD4 exome AF: 0.0267 AC: 8228 AN: 308484 Hom.: 121 Cov.: 0 AF XY: 0.0256 AC XY: 4240 AN XY: 165932

Gnomad4 AFR exome AF: 0.0427

Gnomad4 AMR exome AF: 0.0159

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.0331

Gnomad4 SAS exome AF: 0.0179

Gnomad4 FIN exome AF: 0.0222

Gnomad4 NFE exome AF: 0.0291

Gnomad4 OTH exome AF: 0.0311

GnomAD4 genome AF: 0.0328 AC: 4990 AN: 152198 Hom.: 110 Cov.: 33 AF XY: 0.0320 AC XY: 2382 AN XY: 74406

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0252

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0304

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0192

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0380

Alfa AF: 0.0316 Hom.: 24

Bravo AF: 0.0342

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.79
Cadd	Benign	0.17
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs75126416; hg19: chr17-76988668;