17-78992494-A-G

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.*1056T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 373,490 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (8 hom.)
• Consequence: CANT1 NM_001159773.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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=-0.94).
• BP6: Variant 17-78992494-A-G is Benign according to our data. Variant chr17-78992494-A-G is described in ClinVar as [Benign]. Clinvar id is 325675.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00161 (245/152308) while in subpopulation EAS AF= 0.0382 (198/5182). AF 95% confidence interval is 0.0339. There are 2 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CANT1	NM_001159773.2	c.*1056T>C		3_prime_UTR_variant	5/5	ENST00000392446.10
CANT1	NM_001159772.2	c.*1056T>C		3_prime_UTR_variant	6/6
CANT1	NM_138793.4	c.*1056T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CANT1	ENST00000392446.10	c.*1056T>C		3_prime_UTR_variant	5/5	1	NM_001159773.2	P1
CANT1	ENST00000302345.6	c.*1056T>C		3_prime_UTR_variant	4/4	2		P1
CANT1	ENST00000620915.4	c.*1056T>C		3_prime_UTR_variant	4/4	5		P1
CANT1	ENST00000592228.1	c.*120T>C		3_prime_UTR_variant, NMD_transcript_variant	3/4	5

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152190 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.00250 AC: 552 AN: 221182 Hom.: 8 Cov.: 0 AF XY: 0.00244 AC XY: 281 AN XY: 115138

Gnomad4 AFR exome AF: 0.000502

Gnomad4 AMR exome AF: 0.0000873

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0265

Gnomad4 SAS exome AF: 0.00207

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000478

Gnomad4 OTH exome AF: 0.00175

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152308 Hom.: 2 Cov.: 33 AF XY: 0.00195 AC XY: 145 AN XY: 74486

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0382

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000718 Hom.: 0

Bravo AF: 0.00225

Asia WGS AF: 0.0200 AC: 71 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	-0.94
Cadd	Benign	0.45
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77565945; hg19: chr17-76988576;