rs12666831

Variant names:

• chr7-93437436-T-C
• rs12666831
• NM_001742.4:c.930+624A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-93437436-T-C
• chr7-93437436-T-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.930+624A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,142 control chromosomes in the GnomAD database, including 1,442 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 0.11 (1442 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.930+624A>G		intron_variant	Intron 11 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.978+624A>G		intron_variant	Intron 13 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.930+624A>G		intron_variant	Intron 10 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.930+624A>G		intron_variant	Intron 11 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17108 AN: 152024 Hom.: 1445 Cov.: 32

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.112 AC: 17097 AN: 152142 Hom.: 1442 Cov.: 32 AF XY: 0.116 AC XY: 8653 AN XY: 74394

African (AFR) AF: 0.0561 AC: 2329 AN: 41530

American (AMR) AF: 0.136 AC: 2079 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3470

East Asian (EAS) AF: 0.464 AC: 2391 AN: 5152

South Asian (SAS) AF: 0.208 AC: 1004 AN: 4822

European-Finnish (FIN) AF: 0.0734 AC: 777 AN: 10588

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.108 AC: 7356 AN: 67974

Other (OTH) AF: 0.138 AC: 290 AN: 2108

Alfa AF: 0.105 Hom.: 110

Bravo AF: 0.117

Asia WGS AF: 0.296 AC: 1026 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.78
DANN	Benign	0.54
PhyloP100		0.093
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: rs12666831; hg19: chr7-93066748;