Variant chr7-93426412-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001742.4(CALCR):c.1369G>A(p.Glu457Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,613,848 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 11 hom. )

Consequence

CALCR
NM_001742.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.935

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065184534).

BP6

Variant 7-93426412-C-T is Benign according to our data. Variant chr7-93426412-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043898.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CALCR	NM_001742.4 linkuse as main transcript	c.1369G>A	p.Glu457Lys	missense_variant	14/14	ENST00000426151.7
CALCR	NM_001164737.3 linkuse as main transcript	c.1417G>A	p.Glu473Lys	missense_variant	16/16
CALCR	NM_001164738.2 linkuse as main transcript	c.1369G>A	p.Glu457Lys	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7 linkuse as main transcript	c.1369G>A	p.Glu457Lys	missense_variant	14/14	1	NM_001742.4	P1	P30988-2

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

308

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00342

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00137

AC:

345

AN:

251488

Hom.:

AF XY:

0.00138

AC XY:

187

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00339

AC:

4954

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

2355

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000936

Gnomad4 NFE exome

AF:

0.00410

Gnomad4 OTH exome

AF:

0.00424

GnomAD4 genome

AF:

0.00202

AC:

308

AN:

152280

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00342

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00255

Hom.:

Bravo

AF:

0.00212

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00105

AC:

127

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00279

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CALCR-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.6

DANN

Benign

0.91

DEOGEN2

Benign

0.015

.;T;T;T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.78

T;.;.;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0065

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.18

N;N;N;.;N

REVEL

Benign

0.013

Sift

Benign

0.44

T;T;T;.;T

Sift4G

Benign

0.73

T;T;T;.;T

Vest4

0.092

MVP

0.26

MPC

0.28

ClinPred

0.0028

GERP RS

0.78

gMVP

0.37

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