rs12666751

Positions:

• chr7-93562093-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000426151.7(CALCR):​c.-27+12196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,576 control chromosomes in the GnomAD database, including 36,293 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 0.68 (36293 hom., cov: 30)
• Consequence: CALCR ENST00000426151.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCR	NM_001742.4	c.-27+12196A>G		intron_variant		ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.-98+12196A>G		intron_variant			NP_001158209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.-27+12196A>G		intron_variant		1	NM_001742.4	ENSP00000389295	P1
CALCR	ENST00000649521.1	c.-98+12196A>G		intron_variant				ENSP00000497687

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103062 AN: 151480 Hom.: 36254 Cov.: 30

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.680 AC: 103147 AN: 151576 Hom.: 36293 Cov.: 30 AF XY: 0.677 AC XY: 50105 AN XY: 74042

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.671

Alfa AF: 0.639 Hom.: 4123

Bravo AF: 0.692

Asia WGS AF: 0.681 AC: 2364 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12666751; hg19: chr7-93191405;