rs149628324

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-93426534-C-A
• chr7-93426534-C-G
• chr7-93426534-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001742.4(CALCR):​c.1247G>T​(p.Arg416Leu) 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. 14/20 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. R416H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CALCR NM_001742.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 4 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32431945).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	NM_001742.4	MANE Select	c.1247G>T	p.Arg416Leu	missense	Exon 14 of 14	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.1295G>T	p.Arg432Leu	missense	Exon 16 of 16	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.1247G>T	p.Arg416Leu	missense	Exon 13 of 13	NP_001158210.1	P30988-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	ENST00000426151.7	TSL:1 MANE Select	c.1247G>T	p.Arg416Leu	missense	Exon 14 of 14	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.1247G>T	p.Arg416Leu	missense	Exon 13 of 13	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.*472G>T		non_coding_transcript_exon	Exon 13 of 13	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.84	T
PhyloP100		1.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.047	D
Vest4		0.17
MutPred		0.50		Loss of disorder (P = 0.0369)
MVP		0.74
MPC		0.25
ClinPred		0.86	D
GERP RS		3.8
gMVP		0.71
Mutation Taster		=72/28	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: rs149628324; hg19: chr7-93055846;