rs9641123

Variant names:

• chr7-93568420-G-C
• rs9641123
• NM_001742.4:c.-27+5869C>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.-27+5869C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,640 control chromosomes in the GnomAD database, including 8,180 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 0.30 (8180 hom., cov: 30)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 53 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.-27+5869C>G		intron_variant	Intron 2 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.-98+5869C>G		intron_variant	Intron 2 of 15		NP_001158209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.-27+5869C>G		intron_variant	Intron 2 of 13	1	NM_001742.4	ENSP00000389295.1
CALCR	ENST00000649521.1	c.-98+5869C>G		intron_variant	Intron 1 of 14			ENSP00000497687.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45302 AN: 151522 Hom.: 8183 Cov.: 30

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.299 AC: 45293 AN: 151640 Hom.: 8180 Cov.: 30 AF XY: 0.298 AC XY: 22110 AN XY: 74078

African (AFR) AF: 0.0867 AC: 3583 AN: 41350

American (AMR) AF: 0.277 AC: 4228 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3464

East Asian (EAS) AF: 0.301 AC: 1543 AN: 5118

South Asian (SAS) AF: 0.382 AC: 1834 AN: 4798

European-Finnish (FIN) AF: 0.373 AC: 3913 AN: 10480

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27684 AN: 67864

Other (OTH) AF: 0.321 AC: 676 AN: 2104

Alfa AF: 0.340 Hom.: 1255

Bravo AF: 0.278

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9641123; hg19: chr7-93197732;