rs2283002

Variant names:

• chr7-93430567-C-T
• rs2283002
• NM_001742.4:c.1191+3686G>A

Variant summary

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

The NM_001742.4(CALCR):​c.1191+3686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,072 control chromosomes in the GnomAD database, including 4,215 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 0.23 (4215 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1191+3686G>A		intron_variant	Intron 13 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1239+3686G>A		intron_variant	Intron 15 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.1191+3686G>A		intron_variant	Intron 12 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.1191+3686G>A		intron_variant	Intron 13 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34624 AN: 151954 Hom.: 4206 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.228 AC: 34661 AN: 152072 Hom.: 4215 Cov.: 32 AF XY: 0.234 AC XY: 17406 AN XY: 74344

African (AFR) AF: 0.252 AC: 10448 AN: 41498

American (AMR) AF: 0.326 AC: 4986 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2022 AN: 5172

South Asian (SAS) AF: 0.261 AC: 1260 AN: 4820

European-Finnish (FIN) AF: 0.231 AC: 2435 AN: 10554

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12344 AN: 67968

Other (OTH) AF: 0.229 AC: 484 AN: 2112

Alfa AF: 0.214 Hom.: 1380

Bravo AF: 0.239

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.24
PhyloP100		-0.23
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: rs2283002; hg19: chr7-93059879;