rs7783961

Variant names:

• chr7-93448933-G-T
• rs7783961
• NM_001742.4:c.649-5176C>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.649-5176C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,768 control chromosomes in the GnomAD database, including 5,173 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 0.25 (5173 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	NM_001742.4	MANE Select	c.649-5176C>A		intron	N/A	NP_001733.1
	CALCR	NM_001164737.3		c.697-5176C>A		intron	N/A	NP_001158209.2
	CALCR	NM_001164738.2		c.649-5176C>A		intron	N/A	NP_001158210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	ENST00000426151.7	TSL:1 MANE Select	c.649-5176C>A		intron	N/A	ENSP00000389295.1
	CALCR	ENST00000394441.5	TSL:1	c.649-5176C>A		intron	N/A	ENSP00000377959.1
	CALCR	ENST00000415529.2	TSL:1	n.649-5176C>A		intron	N/A	ENSP00000413179.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38348 AN: 151652 Hom.: 5174 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.253 AC: 38361 AN: 151768 Hom.: 5173 Cov.: 32 AF XY: 0.244 AC XY: 18066 AN XY: 74158

African (AFR) AF: 0.262 AC: 10862 AN: 41394

American (AMR) AF: 0.251 AC: 3824 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1139 AN: 3464

East Asian (EAS) AF: 0.0284 AC: 146 AN: 5146

South Asian (SAS) AF: 0.187 AC: 899 AN: 4818

European-Finnish (FIN) AF: 0.154 AC: 1621 AN: 10552

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18952 AN: 67862

Other (OTH) AF: 0.285 AC: 600 AN: 2108

Alfa AF: 0.271 Hom.: 16230

Bravo AF: 0.261

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.49
PhyloP100		-1.3
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: rs7783961; hg19: chr7-93078245;