7-93426441-A-C

Variant names:

• chr7-93426441-A-C
• rs1801197
• NM_001742.4:c.1340T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001742.4(CALCR):​c.1340T>G​(p.Leu447Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L447P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALCR NM_001742.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06904155).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	NM_001742.4	MANE Select	c.1340T>G	p.Leu447Arg	missense	Exon 14 of 14	NP_001733.1
	CALCR	NM_001164737.3		c.1388T>G	p.Leu463Arg	missense	Exon 16 of 16	NP_001158209.2
	CALCR	NM_001164738.2		c.1340T>G	p.Leu447Arg	missense	Exon 13 of 13	NP_001158210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	ENST00000426151.7	TSL:1 MANE Select	c.1340T>G	p.Leu447Arg	missense	Exon 14 of 14	ENSP00000389295.1
	CALCR	ENST00000394441.5	TSL:1	c.1340T>G	p.Leu447Arg	missense	Exon 13 of 13	ENSP00000377959.1
	CALCR	ENST00000415529.2	TSL:1	n.*565T>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000413179.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.058
Sift	Benign	0.28	T
Sift4G	Benign	0.52	T
Vest4		0.054
MutPred		0.41		Gain of solvent accessibility (P = 0.0039)
MVP		0.29
MPC		0.39
ClinPred		0.064	T
GERP RS		1.3
gMVP		0.33
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1801197; hg19: chr7-93055753;