rs2377301

Positions:

• chr17-78998287-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 BA1

The ENST00000591773.5(CANT1):​c.-285-1G>A variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 157,274 control chromosomes in the GnomAD database, including 1,761 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1709 hom., cov: 33)
  • Exomes 𝑓: 0.14 (52 hom.)
• Consequence: CANT1 ENST00000591773.5 splice_acceptor
• Scores: Splicing: ADA: 0.0001073
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346

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 Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CANT1	NM_001159773.2	c.-146-324G>A		intron_variant		ENST00000392446.10	NP_001153245.1
CANT1	NM_001159772.2	c.-285-1G>A		splice_acceptor_variant			NP_001153244.1
CANT1	NM_138793.4	c.-341-324G>A		intron_variant			NP_620148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CANT1	ENST00000392446.10	c.-146-324G>A		intron_variant		1	NM_001159773.2	ENSP00000376241	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20019 AN: 152158 Hom.: 1700 Cov.: 33

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.138 AC: 690 AN: 4998 Hom.: 52 Cov.: 0 AF XY: 0.135 AC XY: 326 AN XY: 2422

Gnomad4 AFR exome AF: 0.0493

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.0678

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.132 AC: 20030 AN: 152276 Hom.: 1709 Cov.: 33 AF XY: 0.136 AC XY: 10142 AN XY: 74448

Gnomad4 AFR AF: 0.0947

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.129

Alfa AF: 0.128 Hom.: 866

Bravo AF: 0.141

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.3
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0060
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: rs2377301; hg19: chr17-76994369;