7-93563398-T-C

Variant names:

• chr7-93563398-T-C
• rs1548457
• NM_001742.4:c.-27+10891A>G

Variant summary

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

The NM_001164737.3(CALCR):​c.-98+10891A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,138 control chromosomes in the GnomAD database, including 7,785 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 0.29 (7785 hom., cov: 32)
• Consequence: CALCR NM_001164737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	NM_001742.4	MANE Select	c.-27+10891A>G		intron	N/A	NP_001733.1
	CALCR	NM_001164737.3		c.-98+10891A>G		intron	N/A	NP_001158209.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	ENST00000426151.7	TSL:1 MANE Select	c.-27+10891A>G		intron	N/A	ENSP00000389295.1
	CALCR	ENST00000649521.1		c.-98+10891A>G		intron	N/A	ENSP00000497687.1
	CALCR	ENST00000887175.1		c.-27+10891A>G		intron	N/A	ENSP00000557234.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44210 AN: 152022 Hom.: 7787 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.291 AC: 44203 AN: 152138 Hom.: 7785 Cov.: 32 AF XY: 0.291 AC XY: 21648 AN XY: 74358

African (AFR) AF: 0.0847 AC: 3520 AN: 41554

American (AMR) AF: 0.270 AC: 4135 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1301 AN: 3468

East Asian (EAS) AF: 0.302 AC: 1565 AN: 5178

South Asian (SAS) AF: 0.385 AC: 1852 AN: 4806

European-Finnish (FIN) AF: 0.368 AC: 3879 AN: 10550

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26767 AN: 67974

Other (OTH) AF: 0.313 AC: 662 AN: 2112

Alfa AF: 0.327 Hom.: 3230

Bravo AF: 0.270

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.28
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: rs1548457; hg19: chr7-93192710;