rs2298122

chr10-133328068-G-T

Variant summary

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

The NM_015722.4(CALY):c.136-53C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,132,222 control chromosomes in the GnomAD database, including 361,488 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 0.72 (40935 hom., cov: 33)
  • Exomes 𝑓: 0.81 (320553 hom.)
• Consequence: CALY NM_015722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALY	NM_015722.4	c.136-53C>A		intron_variant		ENST00000252939.9
ZNF511-PRAP1	NM_001396060.1	c.680+16227G>T		intron_variant
CALY	NM_001321617.2	c.-271-53C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALY	ENST00000252939.9	c.136-53C>A		intron_variant		1	NM_015722.4	P1
CALY	ENST00000368555.3	c.136-53C>A		intron_variant		2
CALY	ENST00000368558.1	c.136-53C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109304 AN: 151970 Hom.: 40918 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.730

GnomAD4 exome AF: 0.806 AC: 789882 AN: 980134 Hom.: 320553 AF XY: 0.807 AC XY: 405701 AN XY: 502466

Gnomad4 AFR exome AF: 0.482

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.919

Gnomad4 SAS exome AF: 0.814

Gnomad4 FIN exome AF: 0.849

Gnomad4 NFE exome AF: 0.814

Gnomad4 OTH exome AF: 0.782

GnomAD4 genome AF: 0.719 AC: 109348 AN: 152088 Hom.: 40935 Cov.: 33 AF XY: 0.724 AC XY: 53823 AN XY: 74350

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.733

Alfa AF: 0.795 Hom.: 74501

Bravo AF: 0.700

Asia WGS AF: 0.827 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.77
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs2298122; hg19: chr10-135141572; COSMIC: COSV53310694; COSMIC: COSV53310694;