rs12154667

Variant names:

• chr7-93549490-C-T
• rs12154667
• NM_001742.4:c.-27+24799G>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.-27+24799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,876 control chromosomes in the GnomAD database, including 12,138 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 0.38 (12138 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• 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)

LOC105375400 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.-27+24799G>A		intron_variant	Intron 2 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.-98+24799G>A		intron_variant	Intron 2 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.-27+10031G>A		intron_variant	Intron 1 of 12		NP_001158210.1
LOC105375400	XR_927749.3	n.72-1318C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.-27+24799G>A		intron_variant	Intron 2 of 13	1	NM_001742.4	ENSP00000389295.1
CALCR	ENST00000394441.5	c.-27+10031G>A		intron_variant	Intron 1 of 12	1		ENSP00000377959.1
CALCR	ENST00000649521.1	c.-98+24799G>A		intron_variant	Intron 1 of 14			ENSP00000497687.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57782 AN: 151758 Hom.: 12136 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.381 AC: 57799 AN: 151876 Hom.: 12138 Cov.: 32 AF XY: 0.377 AC XY: 28003 AN XY: 74218

African (AFR) AF: 0.203 AC: 8411 AN: 41452

American (AMR) AF: 0.349 AC: 5325 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1871 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1688 AN: 5160

South Asian (SAS) AF: 0.461 AC: 2212 AN: 4798

European-Finnish (FIN) AF: 0.382 AC: 4019 AN: 10526

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32744 AN: 67912

Other (OTH) AF: 0.418 AC: 880 AN: 2104

Alfa AF: 0.402 Hom.: 1735

Bravo AF: 0.368

Asia WGS AF: 0.359 AC: 1246 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.25
PhyloP100		0.25
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: rs12154667; hg19: chr7-93178802;