rs11101694

Variant names:

• chr10-133333210-T-C
• rs11101694
• NM_015722.4:c.-21+3624A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015722.4(CALY):​c.-21+3624A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 144,118 control chromosomes in the GnomAD database, including 2,678 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 0.18 (2678 hom., cov: 26)
• Consequence: CALY NM_015722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 13 publications found

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:38088): (ZNF511-PRAP1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ZNF511 (zinc finger protein 511) and PRAP1 (proline-rich acidic protein 1) genes on chromosome 10. The putative readthrough transcript may encode a fusion protein that shares sequence identity with each individual gene product and may be involved in the regulation of gene promoters, particularly those found on transfected plasmids. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALY	NM_015722.4	c.-21+3624A>G		intron_variant	Intron 1 of 5	ENST00000252939.9	NP_056537.1
ZNF511-PRAP1	NM_001396060.1	c.681-16885T>C		intron_variant	Intron 5 of 8		NP_001382989.1
CALY	NM_001321617.2	c.-427+3624A>G		intron_variant	Intron 1 of 5		NP_001308546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALY	ENST00000252939.9	c.-21+3624A>G		intron_variant	Intron 1 of 5	1	NM_015722.4	ENSP00000252939.4
ZNF511-PRAP1	ENST00000368554.8	c.507-16885T>C		intron_variant	Intron 4 of 7	2		ENSP00000357542.5
CALY	ENST00000368555.3	c.-21+3624A>G		intron_variant	Intron 1 of 2	2		ENSP00000357543.3
CALY	ENST00000368558.1	c.-15+3624A>G		intron_variant	Intron 1 of 4	5		ENSP00000357546.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 25961 AN: 144020 Hom.: 2663 Cov.: 26

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.180 AC: 26003 AN: 144118 Hom.: 2678 Cov.: 26 AF XY: 0.179 AC XY: 12429 AN XY: 69532

African (AFR) AF: 0.268 AC: 10311 AN: 38524

American (AMR) AF: 0.227 AC: 3112 AN: 13732

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 485 AN: 3422

East Asian (EAS) AF: 0.0656 AC: 321 AN: 4894

South Asian (SAS) AF: 0.135 AC: 606 AN: 4502

European-Finnish (FIN) AF: 0.122 AC: 1117 AN: 9172

Middle Eastern (MID) AF: 0.195 AC: 55 AN: 282

European-Non Finnish (NFE) AF: 0.141 AC: 9376 AN: 66714

Other (OTH) AF: 0.185 AC: 368 AN: 1986

Alfa AF: 0.151 Hom.: 2427

Bravo AF: 0.190

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.39
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11101694; hg19: chr10-135146714;