dbSNP rs2298122: CALY:c.136-53C>A (chr10-133328068-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.701

Publications

24 publications found

Variant links:

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]

CALY links:

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]

ZNF511-PRAP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALY	NM_015722.4	MANE Select	c.136-53C>A	intron	N/A	NP_056537.1	Q9NYX4-1
ZNF511-PRAP1	NM_001396060.1		c.680+16227G>T	intron	N/A	NP_001382989.1
CALY	NM_001321617.2		c.-271-53C>A	intron	N/A	NP_001308546.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALY	ENST00000252939.9	TSL:1 MANE Select	c.136-53C>A	intron	N/A	ENSP00000252939.4	Q9NYX4-1
ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.506+16227G>T	intron	N/A	ENSP00000357542.5	H7BY64
CALY	ENST00000956089.1		c.136-53C>A	intron	N/A	ENSP00000626148.1

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109304

AN:

151970

Hom.:

40918

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.482

AC:

11402

AN:

23638

American (AMR)

AF:

0.740

AC:

26526

AN:

35832

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

17580

AN:

22578

East Asian (EAS)

AF:

0.919

AC:

31884

AN:

34706

South Asian (SAS)

AF:

0.814

AC:

58371

AN:

71666

European-Finnish (FIN)

AF:

0.849

AC:

41792

AN:

49248

Middle Eastern (MID)

AF:

0.745

AC:

3619

AN:

4856

European-Non Finnish (NFE)

AF:

0.814

AC:

564233

AN:

693538

Other (OTH)

AF:

0.782

AC:

34475

AN:

44072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8268

16535

24803

33070

41338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10500

21000

31500

42000

52500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.719

AC:

109348

AN:

152088

Hom.:

40935

Cov.:

AF XY:

0.724

AC XY:

53823

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.491

AC:

20342

AN:

41460

American (AMR)

AF:

0.733

AC:

11203

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.774

AC:

2679

AN:

3462

East Asian (EAS)

AF:

0.932

AC:

4816

AN:

5170

South Asian (SAS)

AF:

0.809

AC:

3894

AN:

4816

European-Finnish (FIN)

AF:

0.847

AC:

8973

AN:

10592

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.811

AC:

55132

AN:

67988

Other (OTH)

AF:

0.733

AC:

1544

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1402

2804

4207

5609

7011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.774

Hom.:

121072

Bravo

AF:

0.700

Asia WGS

AF:

0.827

AC:

2876

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.77

(source)

DANN

Benign

0.79

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over