rs10488554

Variant names:

• chr7-93553003-C-T
• rs10488554
• NM_001742.4:c.-27+21286G>A

Variant summary

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

The ENST00000426151.7(CALCR):​c.-27+21286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,058 control chromosomes in the GnomAD database, including 7,191 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 0.28 (7191 hom., cov: 33)
• Consequence: CALCR ENST00000426151.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• 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)

LOC105375400 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000426151.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	NM_001742.4	MANE Select	c.-27+21286G>A		intron	N/A	NP_001733.1
	CALCR	NM_001164737.3		c.-98+21286G>A		intron	N/A	NP_001158209.2
	CALCR	NM_001164738.2		c.-27+6518G>A		intron	N/A	NP_001158210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	ENST00000426151.7	TSL:1 MANE Select	c.-27+21286G>A		intron	N/A	ENSP00000389295.1
	CALCR	ENST00000394441.5	TSL:1	c.-27+6518G>A		intron	N/A	ENSP00000377959.1
	CALCR	ENST00000649521.1		c.-98+21286G>A		intron	N/A	ENSP00000497687.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42537 AN: 151942 Hom.: 7193 Cov.: 33

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.280 AC: 42531 AN: 152058 Hom.: 7191 Cov.: 33 AF XY: 0.280 AC XY: 20795 AN XY: 74304

African (AFR) AF: 0.0825 AC: 3426 AN: 41510

American (AMR) AF: 0.265 AC: 4040 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1301 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1553 AN: 5156

South Asian (SAS) AF: 0.384 AC: 1851 AN: 4820

European-Finnish (FIN) AF: 0.333 AC: 3527 AN: 10580

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25664 AN: 67942

Other (OTH) AF: 0.307 AC: 650 AN: 2114

Alfa AF: 0.289 Hom.: 1125

Bravo AF: 0.262

Asia WGS AF: 0.278 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.75
PhyloP100		0.29
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: rs10488554; hg19: chr7-93182315;