NM_001742.4:c.1150-216C>T

Variant names:

• chr7-93434510-G-A
• rs12669504
• NM_001742.4:c.1150-216C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001742.4(CALCR):​c.1150-216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,584 control chromosomes in the GnomAD database, including 1,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1754 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 7-93434510-G-A is Benign according to our data. Variant chr7-93434510-G-A is described in ClinVar as [Benign]. Clinvar id is 1243075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1150-216C>T		intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1198-216C>T		intron_variant	Intron 14 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.1150-216C>T		intron_variant	Intron 11 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.1150-216C>T		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20286 AN: 151466 Hom.: 1751 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.134 AC: 20304 AN: 151584 Hom.: 1754 Cov.: 32 AF XY: 0.137 AC XY: 10158 AN XY: 74078

African (AFR) AF: 0.130 AC: 5391 AN: 41376

American (AMR) AF: 0.142 AC: 2163 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 685 AN: 3462

East Asian (EAS) AF: 0.468 AC: 2401 AN: 5132

South Asian (SAS) AF: 0.212 AC: 1005 AN: 4750

European-Finnish (FIN) AF: 0.0739 AC: 773 AN: 10456

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7382 AN: 67892

Other (OTH) AF: 0.153 AC: 321 AN: 2104

Alfa AF: 0.119 Hom.: 279

Bravo AF: 0.141

Asia WGS AF: 0.301 AC: 1044 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.64
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: rs12669504; hg19: chr7-93063822;