7-93449088-A-C

Variant names:

• chr7-93449088-A-C
• rs2188805
• NM_001742.4:c.649-5331T>G

Variant summary

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

The NM_001742.4(CALCR):​c.649-5331T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,904 control chromosomes in the GnomAD database, including 10,032 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 0.35 (10032 hom., cov: 33)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.649-5331T>G		intron_variant	Intron 8 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.697-5331T>G		intron_variant	Intron 10 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.649-5331T>G		intron_variant	Intron 7 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.649-5331T>G		intron_variant	Intron 8 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53514 AN: 151786 Hom.: 10021 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.353 AC: 53588 AN: 151904 Hom.: 10032 Cov.: 33 AF XY: 0.345 AC XY: 25613 AN XY: 74262

African (AFR) AF: 0.454 AC: 18813 AN: 41446

American (AMR) AF: 0.408 AC: 6214 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3468

East Asian (EAS) AF: 0.133 AC: 685 AN: 5152

South Asian (SAS) AF: 0.225 AC: 1088 AN: 4828

European-Finnish (FIN) AF: 0.239 AC: 2531 AN: 10582

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21891 AN: 67884

Other (OTH) AF: 0.365 AC: 770 AN: 2110

Alfa AF: 0.327 Hom.: 2473

Bravo AF: 0.374

Asia WGS AF: 0.228 AC: 795 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.2
DANN	Benign	0.84
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: rs2188805; hg19: chr7-93078400;