Genetic Variant CALCR:p.Asn453ThrfsTer13 (chr7-93426422-GT-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001742.4(CALCR):c.1358delA(p.Asn453ThrfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000379 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

CALCR
NM_001742.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.378

Variant links:

Genes affected

CALCR (HGNC:1440): (calcitonin receptor) This gene encodes a high affinity receptor for the peptide hormone calcitonin and belongs to a subfamily of seven transmembrane-spanning G protein-coupled receptors. The encoded protein is involved in maintaining calcium homeostasis and in regulating osteoclast-mediated bone resorption. Polymorphisms in this gene have been associated with variations in bone mineral density and onset of osteoporosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

CALCR links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4 link	c.1358delA	p.Asn453ThrfsTer13	frameshift_variant	Exon 14 of 14	ENST00000426151.7	NP_001733.1	P30988-2
CALCR	NM_001164737.3 link	c.1406delA	p.Asn469ThrfsTer13	frameshift_variant	Exon 16 of 16		NP_001158209.2	P30988-1
CALCR	NM_001164738.2 link	c.1358delA	p.Asn453ThrfsTer13	frameshift_variant	Exon 13 of 13		NP_001158210.1	P30988-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7 link	c.1358delA	p.Asn453ThrfsTer13	frameshift_variant	Exon 14 of 14	1	NM_001742.4	ENSP00000389295.1		P30988-2

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000207

AC:

AN:

251494

AF XY:

0.000206

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000439

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000395

AC:

577

AN:

1461666

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

289

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

AC:

AN:

33472

Gnomad4 AMR exome

AF:

0.0000447

AC:

AN:

44722

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39696

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

86248

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.000505

AC:

561

AN:

1111822

Gnomad4 Remaining exome

AF:

0.000182

AC:

AN:

60382

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

100

<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:

0.000223

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0000722

AC:

0.0000721674

AN:

0.0000721674

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000456

AC:

0.000455668

AN:

0.000455668

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.0000476

Hom.:

Bravo

AF:

0.000227

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 22, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: CALCR c.1358delA (p.Asn453ThrfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein. However, clinical and functional evidence currently available does not allow for definitive conclusions on whether loss-of-function variants in the CALCR gene cause disease. The variant allele was found at a frequency of 0.00021 in 251494 control chromosomes (52/251494 chromosomes from the gnomAD database). To our knowledge, no occurrence of c.1358delA in individuals affected with Postmenopausal Osteoporosis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=58/142

disease causing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over