chr17-78992110-C-T

Variant names:

• chr17-78992110-C-T
• rs4861
• NM_001159773.2:c.*1440G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.57
• Publications: 19 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 -20 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 VariationId is 325669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

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.*1440G>A		3_prime_UTR	Exon 5 of 5	NP_001153245.1	Q8WVQ1-1
	CANT1	NM_001159772.2		c.*1440G>A		3_prime_UTR	Exon 6 of 6	NP_001153244.1	Q8WVQ1-1
	CANT1	NM_138793.4		c.*1440G>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.*1440G>A		3_prime_UTR	Exon 5 of 5	ENSP00000376241.4	Q8WVQ1-1
	CANT1	ENST00000302345.6	TSL:2	c.*1440G>A		3_prime_UTR	Exon 4 of 4	ENSP00000307674.2	Q8WVQ1-1
	CANT1	ENST00000620915.4	TSL:5	c.*1440G>A		3_prime_UTR	Exon 4 of 4	ENSP00000477798.1	Q8WVQ1-1

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

African (AFR) AF: 0.137 AC: 526 AN: 3828

American (AMR) AF: 0.290 AC: 715 AN: 2464

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 417 AN: 5052

East Asian (EAS) AF: 0.256 AC: 2893 AN: 11284

South Asian (SAS) AF: 0.256 AC: 179 AN: 700

European-Finnish (FIN) AF: 0.0625 AC: 4 AN: 64

Middle Eastern (MID) AF: 0.0938 AC: 45 AN: 480

European-Non Finnish (NFE) AF: 0.110 AC: 5440 AN: 49422

Other (OTH) AF: 0.134 AC: 894 AN: 6674

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

African (AFR) AF: 0.144 AC: 5973 AN: 41546

American (AMR) AF: 0.265 AC: 4049 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 323 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1595 AN: 5172

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4818

European-Finnish (FIN) AF: 0.0935 AC: 992 AN: 10610

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7859 AN: 68006

Other (OTH) AF: 0.145 AC: 306 AN: 2112

Alfa AF: 0.128 Hom.: 3289

Bravo AF: 0.159

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Desbuquois dysplasia 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs4861; hg19: chr17-76988192;