chr7-93524748-C-G

Variant names:

• chr7-93524748-C-G
• rs6465387
• NM_001742.4:c.-26-37741G>C

Variant summary

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

The NM_001742.4(CALCR):​c.-26-37741G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,904 control chromosomes in the GnomAD database, including 9,216 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 0.24 (9216 hom., cov: 31)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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.-26-37741G>C		intron	N/A	NP_001733.1
	CALCR	NM_001164737.3		c.-97-28774G>C		intron	N/A	NP_001158209.2
	CALCR	NM_001164738.2		c.-27+34773G>C		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.-26-37741G>C		intron	N/A	ENSP00000389295.1
	CALCR	ENST00000394441.5	TSL:1	c.-27+34773G>C		intron	N/A	ENSP00000377959.1
	CALCR	ENST00000649521.1		c.-97-28774G>C		intron	N/A	ENSP00000497687.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35932 AN: 151784 Hom.: 9190 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.237 AC: 36009 AN: 151904 Hom.: 9216 Cov.: 31 AF XY: 0.239 AC XY: 17714 AN XY: 74256

African (AFR) AF: 0.627 AC: 25930 AN: 41348

American (AMR) AF: 0.236 AC: 3598 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0528 AC: 183 AN: 3466

East Asian (EAS) AF: 0.355 AC: 1835 AN: 5166

South Asian (SAS) AF: 0.162 AC: 783 AN: 4820

European-Finnish (FIN) AF: 0.0720 AC: 760 AN: 10554

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0355 AC: 2414 AN: 67970

Other (OTH) AF: 0.204 AC: 430 AN: 2106

Alfa AF: 0.0142 Hom.: 16

Bravo AF: 0.267

Asia WGS AF: 0.296 AC: 1029 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.4
DANN	Benign	0.83
PhyloP100		0.020
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: rs6465387; hg19: chr7-93154060;