rs12666751

Variant names:

• chr7-93562093-T-C
• rs12666751
• NM_001742.4:c.-27+12196A>G

Variant summary

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

The NM_001742.4(CALCR):​c.-27+12196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,576 control chromosomes in the GnomAD database, including 36,293 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 0.68 (36293 hom., cov: 30)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 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.-27+12196A>G		intron	N/A	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.-98+12196A>G		intron	N/A	NP_001158209.2	A0A0A0MSQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	ENST00000426151.7	TSL:1 MANE Select	c.-27+12196A>G		intron	N/A	ENSP00000389295.1	P30988-2
	CALCR	ENST00000649521.1		c.-98+12196A>G		intron	N/A	ENSP00000497687.1	P30988-1
	CALCR	ENST00000887175.1		c.-27+12196A>G		intron	N/A	ENSP00000557234.1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103062 AN: 151480 Hom.: 36254 Cov.: 30

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.680 AC: 103147 AN: 151576 Hom.: 36293 Cov.: 30 AF XY: 0.677 AC XY: 50105 AN XY: 74042

African (AFR) AF: 0.874 AC: 36148 AN: 41382

American (AMR) AF: 0.618 AC: 9383 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2380 AN: 3466

East Asian (EAS) AF: 0.689 AC: 3551 AN: 5154

South Asian (SAS) AF: 0.658 AC: 3153 AN: 4790

European-Finnish (FIN) AF: 0.541 AC: 5637 AN: 10412

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40684 AN: 67874

Other (OTH) AF: 0.671 AC: 1408 AN: 2098

Alfa AF: 0.647 Hom.: 4392

Bravo AF: 0.692

Asia WGS AF: 0.681 AC: 2364 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.76
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12666751; hg19: chr7-93191405;