NM_001742.4:c.1340T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001742.4(CALCR):c.1340T>C(p.Leu447Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,612,250 control chromosomes in the GnomAD database, including 92,486 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11947 hom., cov: 32)

Exomes 𝑓: 0.31 ( 80539 hom. )

Consequence

CALCR
NM_001742.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 1.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.341892E-7).

BP6

Variant 7-93426441-A-G is Benign according to our data. Variant chr7-93426441-A-G is described in ClinVar as [Benign]. Clinvar id is 17636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4 link	c.1340T>C	p.Leu447Pro	missense_variant	Exon 14 of 14	ENST00000426151.7	NP_001733.1	P30988-2
CALCR	NM_001164737.3 link	c.1388T>C	p.Leu463Pro	missense_variant	Exon 16 of 16		NP_001158209.2	P30988-1
CALCR	NM_001164738.2 link	c.1340T>C	p.Leu447Pro	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.1340T>C	p.Leu447Pro	missense_variant	Exon 14 of 14	1	NM_001742.4	ENSP00000389295.1		P30988-2

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55853

AN:

151764

Hom.:

11927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.386

AC:

97049

AN:

251462

Hom.:

22550

AF XY:

0.379

AC XY:

51556

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.325

Gnomad EAS exome

AF:

0.860

Gnomad SAS exome

AF:

0.487

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.306

AC:

447097

AN:

1460368

Hom.:

80539

Cov.:

AF XY:

0.310

AC XY:

225437

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.875

Gnomad4 SAS exome

AF:

0.489

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.257

Gnomad4 OTH exome

AF:

0.348

GnomAD4 genome

AF:

0.368

AC:

55920

AN:

151882

Hom.:

11947

Cov.:

AF XY:

0.377

AC XY:

27990

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.484

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.857

Gnomad4 SAS

AF:

0.503

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.299

Hom.:

19119

Bravo

AF:

0.388

TwinsUK

AF:

0.260

AC:

963

ALSPAC

AF:

0.258

AC:

993

ESP6500AA

AF:

0.470

AC:

2073

ESP6500EA

AF:

0.254

AC:

2187

ExAC

AF:

0.380

AC:

46137

Asia WGS

AF:

0.673

AC:

2338

AN:

3478

EpiCase

AF:

0.262

EpiControl

AF:

0.265

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 9675109) -

CALCR-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Bone mineral density quantitative trait locus 15

Other:1

Dec 01, 1998

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.036

DEOGEN2

Benign

0.0066

.;T;T;T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.098

T;.;.;T;T

MetaRNN

Benign

9.3e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

1.8

N;N;N;.;N

REVEL

Benign

0.040

Sift

Benign

1.0

T;T;T;.;T

Sift4G

Benign

0.48

T;T;T;.;T

Vest4

0.023

MPC

0.30

ClinPred

0.00052

GERP RS

1.3

gMVP

0.28

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