Genetic Variant CALCR:c.-6T>A (chr7-93486987-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001742.4(CALCR):c.-6T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CALCR
NM_001742.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.180

Publications

34 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035526574).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CALCR	NM_001742.4	MANE Select	c.-6T>A	5_prime_UTR	Exon 3 of 14	NP_001733.1
CALCR	NM_001164737.3		c.-6T>A	5_prime_UTR	Exon 4 of 16	NP_001158209.2
CALCR	NM_001164738.2		c.-6T>A	5_prime_UTR	Exon 2 of 13	NP_001158210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CALCR	ENST00000426151.7	TSL:1 MANE Select	c.-6T>A	5_prime_UTR	Exon 3 of 14	ENSP00000389295.1
CALCR	ENST00000394441.5	TSL:1	c.-6T>A	5_prime_UTR	Exon 2 of 13	ENSP00000377959.1
CALCR	ENST00000649521.1		c.-6T>A	5_prime_UTR	Exon 3 of 15	ENSP00000497687.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151234

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

244898

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1439580

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716992

African (AFR)

AF:

0.00

AC:

AN:

32518

American (AMR)

AF:

0.00

AC:

AN:

43960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25802

East Asian (EAS)

AF:

0.00

AC:

AN:

39316

South Asian (SAS)

AF:

0.00

AC:

AN:

84462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095144

Other (OTH)

AF:

0.00

AC:

AN:

59518

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73822

African (AFR)

AF:

0.00

AC:

AN:

41268

American (AMR)

AF:

0.00

AC:

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5108

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67520

Other (OTH)

AF:

0.00

AC:

AN:

2078

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.7

(source)

DANN

Benign

0.83

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.19

M_CAP

Benign

0.0034

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

PhyloP100

-0.18

PROVEAN

Benign

0.070

REVEL

Benign

0.014

Sift

Benign

0.036

Sift4G

Benign

0.70

Vest4

0.097

MutPred

0.17

Gain of helix (P = 0.0199)

MVP

0.41

MPC

0.17

ClinPred

0.080

GERP RS

0.093

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over