rs10282285

Variant names:

• chr7-93493855-C-T
• rs10282285
• NM_001742.4:c.-26-6848G>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.-26-6848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,352 control chromosomes in the GnomAD database, including 5,843 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 0.18 (5843 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.-26-6848G>A		intron_variant	Intron 2 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.-27+2049G>A		intron_variant	Intron 3 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.-26-6848G>A		intron_variant	Intron 1 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.-26-6848G>A		intron_variant	Intron 2 of 13	1	NM_001742.4	ENSP00000389295.1
CALCR	ENST00000394441.5	c.-26-6848G>A		intron_variant	Intron 1 of 12	1		ENSP00000377959.1
CALCR	ENST00000649521.1	c.-27+2049G>A		intron_variant	Intron 2 of 14			ENSP00000497687.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26815 AN: 151234 Hom.: 5814 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0348

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.178 AC: 26896 AN: 151352 Hom.: 5843 Cov.: 32 AF XY: 0.178 AC XY: 13174 AN XY: 73974

African (AFR) AF: 0.506 AC: 20915 AN: 41348

American (AMR) AF: 0.126 AC: 1904 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.0348 AC: 120 AN: 3444

East Asian (EAS) AF: 0.287 AC: 1465 AN: 5106

South Asian (SAS) AF: 0.0976 AC: 470 AN: 4818

European-Finnish (FIN) AF: 0.0481 AC: 511 AN: 10622

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0173 AC: 1167 AN: 67570

Other (OTH) AF: 0.144 AC: 303 AN: 2100

Alfa AF: 0.102 Hom.: 933

Bravo AF: 0.197

Asia WGS AF: 0.240 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.072
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: rs10282285; hg19: chr7-93123167;