rs1468180

Variant names:

• chr7-93485563-A-G
• rs1468180
• NM_001742.4:c.51+1368T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001742.4(CALCR):​c.51+1368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,348 control chromosomes in the GnomAD database, including 12,958 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12958 hom., cov: 31)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

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.51+1368T>C		intron	N/A	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.51+1368T>C		intron	N/A	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.51+1368T>C		intron	N/A	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.51+1368T>C		intron	N/A	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.51+1368T>C		intron	N/A	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.51+1368T>C		intron	N/A	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60850 AN: 151230 Hom.: 12953 Cov.: 31

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 60872 AN: 151348 Hom.: 12958 Cov.: 31 AF XY: 0.397 AC XY: 29353 AN XY: 73916

African (AFR) AF: 0.279 AC: 11539 AN: 41386

American (AMR) AF: 0.331 AC: 4998 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1702 AN: 3456

East Asian (EAS) AF: 0.403 AC: 2057 AN: 5108

South Asian (SAS) AF: 0.486 AC: 2336 AN: 4808

European-Finnish (FIN) AF: 0.404 AC: 4258 AN: 10534

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32477 AN: 67630

Other (OTH) AF: 0.420 AC: 883 AN: 2100

Alfa AF: 0.430 Hom.: 1889

Bravo AF: 0.389

Asia WGS AF: 0.384 AC: 1324 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.90
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs1468180; hg19: chr7-93114875;