Genetic Variant CALCR:p.Ala429Ser (chr7-93426496-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001742.4(CALCR):c.1285G>T(p.Ala429Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,613,770 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

CALCR
NM_001742.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0250

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

osteoporosis
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CALCR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.00876224).

BP6

Variant 7-93426496-C-A is Benign according to our data. Variant chr7-93426496-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 731330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4 link	c.1285G>T	p.Ala429Ser	missense_variant	Exon 14 of 14	ENST00000426151.7	NP_001733.1	P30988-2
CALCR	NM_001164737.3 link	c.1333G>T	p.Ala445Ser	missense_variant	Exon 16 of 16		NP_001158209.2	P30988-1
CALCR	NM_001164738.2 link	c.1285G>T	p.Ala429Ser	missense_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.1285G>T	p.Ala429Ser	missense_variant	Exon 14 of 14	1	NM_001742.4	ENSP00000389295.1		P30988-2

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00688

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000624

AC:

157

AN:

251402

AF XY:

0.000442

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000200

AC:

293

AN:

1461518

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

138

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.00702

AC:

235

AN:

33468

American (AMR)

AF:

0.000581

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111692

Other (OTH)

AF:

0.000414

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152252

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00688

AC:

286

AN:

41548

American (AMR)

AF:

0.000914

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.00233

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000766

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.28

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0075

.;T;T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.55

T;.;.;T;T

MetaRNN

Benign

0.0088

T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

-0.025

PrimateAI

Benign

0.35

PROVEAN

Benign

0.60

N;N;N;.;N

REVEL

Benign

0.099

Sift

Benign

0.68

T;T;T;.;T

Sift4G

Benign

0.53

T;T;T;.;T

Vest4

0.11

MVP

0.75

MPC

0.19

ClinPred

0.039

GERP RS

4.2

gMVP

0.39

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-93426496-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over