chr7-93426516-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001742.4(CALCR):ā€‹c.1265C>Gā€‹(p.Ser422Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CALCR
NM_001742.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.552
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15080062).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CALCRNM_001742.4 linkuse as main transcriptc.1265C>G p.Ser422Cys missense_variant 14/14 ENST00000426151.7
CALCRNM_001164737.3 linkuse as main transcriptc.1313C>G p.Ser438Cys missense_variant 16/16
CALCRNM_001164738.2 linkuse as main transcriptc.1265C>G p.Ser422Cys missense_variant 13/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CALCRENST00000426151.7 linkuse as main transcriptc.1265C>G p.Ser422Cys missense_variant 14/141 NM_001742.4 P1P30988-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251292
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461712
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727170
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 21, 2023The c.1265C>G (p.S422C) alteration is located in exon 14 (coding exon 12) of the CALCR gene. This alteration results from a C to G substitution at nucleotide position 1265, causing the serine (S) at amino acid position 422 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
13
DANN
Uncertain
0.98
DEOGEN2
Benign
0.058
.;T;T;T;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.062
N
LIST_S2
Benign
0.62
T;.;.;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.15
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.8
N;N;N;.;N
REVEL
Benign
0.034
Sift
Benign
0.041
D;D;D;.;D
Sift4G
Uncertain
0.037
D;D;D;.;D
Vest4
0.12
MutPred
0.38
.;.;Loss of disorder (P = 0.0041);.;Loss of disorder (P = 0.0041);
MVP
0.66
MPC
0.53
ClinPred
0.25
T
GERP RS
-1.3
gMVP
0.44

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.

Other links and lift over

dbSNP: rs370893082; hg19: chr7-93055828; API