rs2214213

Positions:

• chr7-93448748-T-C

Variant summary

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

The NM_001742.4(CALCR):​c.649-4991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,876 control chromosomes in the GnomAD database, including 32,887 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 0.65 (32887 hom., cov: 33)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.649-4991A>G		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.697-4991A>G		intron_variant
CALCR	NM_001164738.2	c.649-4991A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.649-4991A>G		intron_variant		1	NM_001742.4	P1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98181 AN: 151760 Hom.: 32833 Cov.: 33

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.647 AC: 98299 AN: 151876 Hom.: 32887 Cov.: 33 AF XY: 0.643 AC XY: 47731 AN XY: 74198

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.647

Alfa AF: 0.588 Hom.: 37761

Bravo AF: 0.664

Asia WGS AF: 0.601 AC: 2089 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.75
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2214213; hg19: chr7-93078060;