rs2275723

chr10-133326131-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015722.4(CALY):c.361-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,591,104 control chromosomes in the GnomAD database, including 9,526 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.091 (794 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8732 hom.)
• Consequence: CALY NM_015722.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005574
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

Genes affected

CALY (HGNC:17938): (calcyon neuron specific vesicular protein) The protein encoded by this gene is a type II single transmembrane protein. It is required for maximal stimulated calcium release after stimulation of purinergic or muscarinic but not beta-adrenergic receptors. The encoded protein interacts with D1 dopamine receptor and may interact with other DA receptor subtypes and/or GPCRs. [provided by RefSeq, Jul 2008]

ZNF511-PRAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALY	NM_015722.4	c.361-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000252939.9
ZNF511-PRAP1	NM_001396060.1	c.680+14290G>A		intron_variant
CALY	NM_001321617.2	c.104C>T	p.Pro35Leu	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALY	ENST00000252939.9	c.361-11C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015722.4	P1
CALY	ENST00000368558.1	c.*135C>T		3_prime_UTR_variant	5/5	5
CALY	ENST00000467433.5	n.45C>T		non_coding_transcript_exon_variant	1/2	3
CALY	ENST00000467611.1	n.184C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13866 AN: 152122 Hom.: 790 Cov.: 33

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.106 AC: 24005 AN: 226346 Hom.: 1518 AF XY: 0.104 AC XY: 12943 AN XY: 124072

Gnomad AFR exome AF: 0.0430

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.0772

Gnomad EAS exome AF: 0.0347

Gnomad SAS exome AF: 0.100

Gnomad FIN exome AF: 0.0748

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.106 AC: 153088 AN: 1438864 Hom.: 8732 Cov.: 32 AF XY: 0.106 AC XY: 75403 AN XY: 712566

Gnomad4 AFR exome AF: 0.0421

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.0758

Gnomad4 EAS exome AF: 0.0563

Gnomad4 SAS exome AF: 0.0958

Gnomad4 FIN exome AF: 0.0774

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0912 AC: 13883 AN: 152240 Hom.: 794 Cov.: 33 AF XY: 0.0900 AC XY: 6697 AN XY: 74434

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.0484

Gnomad4 SAS AF: 0.0960

Gnomad4 FIN AF: 0.0714

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.101

Alfa AF: 0.106 Hom.: 987

Bravo AF: 0.0953

Asia WGS AF: 0.0880 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	12
Dann	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000056
dbscSNV1_RF	Benign	0.0
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: rs2275723; hg19: chr10-135139635; COSMIC: COSV53310633; COSMIC: COSV53310633;