7-93426534-C-G

Variant names:

• chr7-93426534-C-G
• rs149628324
• NM_001742.4:c.1247G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001742.4(CALCR):​c.1247G>C​(p.Arg416Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,368 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CALCR NM_001742.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3568756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1247G>C	p.Arg416Pro	missense_variant	Exon 14 of 14	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1295G>C	p.Arg432Pro	missense_variant	Exon 16 of 16		NP_001158209.2
CALCR	NM_001164738.2	c.1247G>C	p.Arg416Pro	missense_variant	Exon 13 of 13		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.1247G>C	p.Arg416Pro	missense_variant	Exon 14 of 14	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461368 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726940

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: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	.;T;T;T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	T;.;.;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N;N;N;.;N
REVEL	Benign	0.17
Sift	Uncertain	0.023	D;D;D;.;D
Sift4G	Uncertain	0.040	D;D;D;.;D
Vest4		0.28
MutPred		0.51		.;.;Gain of glycosylation at R416 (P = 0.0245);.;Gain of glycosylation at R416 (P = 0.0245);
MVP		0.82
MPC		0.29
ClinPred		0.78	D
GERP RS		3.8
gMVP		0.79

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

Other links and lift over

dbSNP: rs149628324; hg19: chr7-93055846;