chr7-93426534-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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)
• 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=0.32431945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1247G>T	p.Arg416Leu	missense_variant	Exon 14 of 14	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1295G>T	p.Arg432Leu	missense_variant	Exon 16 of 16		NP_001158209.2
CALCR	NM_001164738.2	c.1247G>T	p.Arg416Leu	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>T	p.Arg416Leu	missense_variant	Exon 14 of 14	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.84	T;.;.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.84	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N;N;N;.;N
REVEL	Benign	0.15
Sift	Uncertain	0.027	D;D;D;.;D
Sift4G	Uncertain	0.047	D;T;T;.;T
Vest4		0.17
MutPred		0.50		.;.;Loss of disorder (P = 0.0369);.;Loss of disorder (P = 0.0369);
MVP		0.74
MPC		0.25
ClinPred		0.86	D
GERP RS		3.8
gMVP		0.71

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;