17-78992074-C-T

Variant names:

• chr17-78992074-C-T
• rs73999357
• NM_001159773.2:c.*1476G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001159773.2(CANT1):​c.*1476G>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 0.00341 in 232,066 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00099 (0 hom.)
• Consequence: CANT1 NM_001159773.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.628
• Publications: 0 publications found

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]

CANT1 Gene-Disease associations (from GenCC):

• Desbuquois dysplasia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Desbuquois dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-78992074-C-T is Benign according to our data. Variant chr17-78992074-C-T is described in ClinVar as Benign. ClinVar VariationId is 325668.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00467 (712/152308) while in subpopulation AFR AF = 0.0159 (660/41558). AF 95% confidence interval is 0.0149. There are 6 homozygotes in GnomAd4. There are 354 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159773.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	NM_001159773.2	MANE Select	c.*1476G>A		3_prime_UTR	Exon 5 of 5	NP_001153245.1	Q8WVQ1-1
	CANT1	NM_001159772.2		c.*1476G>A		3_prime_UTR	Exon 6 of 6	NP_001153244.1	Q8WVQ1-1
	CANT1	NM_138793.4		c.*1476G>A		3_prime_UTR	Exon 4 of 4	NP_620148.1	Q8WVQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	ENST00000392446.10	TSL:1 MANE Select	c.*1476G>A		3_prime_UTR	Exon 5 of 5	ENSP00000376241.4	Q8WVQ1-1
	CANT1	ENST00000302345.6	TSL:2	c.*1476G>A		3_prime_UTR	Exon 4 of 4	ENSP00000307674.2	Q8WVQ1-1
	CANT1	ENST00000620915.4	TSL:5	c.*1476G>A		3_prime_UTR	Exon 4 of 4	ENSP00000477798.1	Q8WVQ1-1

Frequencies

GnomAD3 genomes AF: 0.00470 AC: 715 AN: 152190 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000990 AC: 79 AN: 79758 Hom.: 0 Cov.: 0 AF XY: 0.000899 AC XY: 33 AN XY: 36706

African (AFR) AF: 0.0147 AC: 56 AN: 3814

American (AMR) AF: 0.00205 AC: 5 AN: 2440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5048

East Asian (EAS) AF: 0.00 AC: 0 AN: 11274

South Asian (SAS) AF: 0.00 AC: 0 AN: 690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 64

Middle Eastern (MID) AF: 0.00413 AC: 2 AN: 484

European-Non Finnish (NFE) AF: 0.0000609 AC: 3 AN: 49276

Other (OTH) AF: 0.00195 AC: 13 AN: 6668

GnomAD4 genome AF: 0.00467 AC: 712 AN: 152308 Hom.: 6 Cov.: 33 AF XY: 0.00475 AC XY: 354 AN XY: 74468

African (AFR) AF: 0.0159 AC: 660 AN: 41558

American (AMR) AF: 0.00229 AC: 35 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68030

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00259 Hom.: 1

Bravo AF: 0.00550

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Desbuquois dysplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.72
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73999357; hg19: chr17-76988156;