17-78992110-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001159773.2(CANT1):c.*1440G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 232,206 control chromosomes in the GnomAD database, including 2,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2024 hom., cov: 33)
  • Exomes 𝑓: 0.14 (938 hom.)
• Consequence: CANT1 NM_001159773.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

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=-0.88).
• BP6: Variant 17-78992110-C-T is Benign according to our data. Variant chr17-78992110-C-T is described in ClinVar as [Benign]. Clinvar id is 325669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CANT1	NM_001159773.2	c.*1440G>A		3_prime_UTR_variant	5/5	ENST00000392446.10
CANT1	NM_001159772.2	c.*1440G>A		3_prime_UTR_variant	6/6
CANT1	NM_138793.4	c.*1440G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CANT1	ENST00000392446.10	c.*1440G>A		3_prime_UTR_variant	5/5	1	NM_001159773.2	P1
CANT1	ENST00000302345.6	c.*1440G>A		3_prime_UTR_variant	4/4	2		P1
CANT1	ENST00000620915.4	c.*1440G>A		3_prime_UTR_variant	4/4	5		P1
CANT1	ENST00000592228.1	c.*235G>A		3_prime_UTR_variant, NMD_transcript_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22438 AN: 152120 Hom.: 2015 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.139 AC: 11113 AN: 79968 Hom.: 938 Cov.: 0 AF XY: 0.140 AC XY: 5136 AN XY: 36800

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.0825

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.147 AC: 22453 AN: 152238 Hom.: 2024 Cov.: 33 AF XY: 0.152 AC XY: 11277 AN XY: 74434

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.0930

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.0935

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.145

Alfa AF: 0.121 Hom.: 1595

Bravo AF: 0.159

Asia WGS AF: 0.274 AC: 951 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	-0.88
Cadd	Benign	4.2
Dann	Benign	0.79

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: rs4861; hg19: chr17-76988192;