chr7-93463746-C-T

Variant names:

• chr7-93463746-C-T
• rs2299249
• NM_001742.4:c.522-2799G>A

Variant summary

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

The NM_001164737.3(CALCR):​c.522-1636G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,714 control chromosomes in the GnomAD database, including 12,990 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 0.40 (12990 hom., cov: 32)
• Consequence: CALCR NM_001164737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 0 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 (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164737.3. 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.522-2799G>A		intron	N/A	NP_001733.1
	CALCR	NM_001164737.3		c.522-1636G>A		intron	N/A	NP_001158209.2
	CALCR	NM_001164738.2		c.522-2799G>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.522-2799G>A		intron	N/A	ENSP00000389295.1
	CALCR	ENST00000394441.5	TSL:1	c.522-2799G>A		intron	N/A	ENSP00000377959.1
	CALCR	ENST00000415529.2	TSL:1	n.522-2799G>A		intron	N/A	ENSP00000413179.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61057 AN: 151596 Hom.: 12985 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.403 AC: 61079 AN: 151714 Hom.: 12990 Cov.: 32 AF XY: 0.398 AC XY: 29471 AN XY: 74136

African (AFR) AF: 0.280 AC: 11596 AN: 41452

American (AMR) AF: 0.331 AC: 5037 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2077 AN: 5136

South Asian (SAS) AF: 0.487 AC: 2343 AN: 4816

European-Finnish (FIN) AF: 0.404 AC: 4268 AN: 10554

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32537 AN: 67778

Other (OTH) AF: 0.423 AC: 887 AN: 2098

Alfa AF: 0.431 Hom.: 1966

Bravo AF: 0.389

Asia WGS AF: 0.385 AC: 1341 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	1.2
DANN	Benign	0.61
PhyloP100		-0.19
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: rs2299249; hg19: chr7-93093058;