7-93434389-G-GA

Variant names:

• chr7-93434389-G-GA
• rs200558502
• NM_001742.4:c.1150-96dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001742.4(CALCR):​c.1150-96dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 492,844 control chromosomes in the GnomAD database, including 3,746 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3412 hom., cov: 0)
  • Exomes 𝑓: 0.21 (334 hom.)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.590
• 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 -10 ACMG points.

• BP6: Variant 7-93434389-G-GA is Benign according to our data. Variant chr7-93434389-G-GA is described in ClinVar as [Benign]. Clinvar id is 1243938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1150-96dupT		intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1198-96dupT		intron_variant	Intron 14 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.1150-96dupT		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.1150-96_1150-95insT		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 27110 AN: 135470 Hom.: 3411 Cov.: 0

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.273

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.207 AC: 73851 AN: 357336 Hom.: 334 AF XY: 0.207 AC XY: 39108 AN XY: 189156

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.299 AC: 3124 AN: 10444

American (AMR) AF: 0.215 AC: 3297 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 2864 AN: 11842

East Asian (EAS) AF: 0.391 AC: 10029 AN: 25676

South Asian (SAS) AF: 0.234 AC: 6661 AN: 28508

European-Finnish (FIN) AF: 0.140 AC: 3712 AN: 26444

Middle Eastern (MID) AF: 0.233 AC: 464 AN: 1992

European-Non Finnish (NFE) AF: 0.180 AC: 39041 AN: 216326

Other (OTH) AF: 0.224 AC: 4659 AN: 20804

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.200 AC: 27120 AN: 135508 Hom.: 3412 Cov.: 0 AF XY: 0.203 AC XY: 13269 AN XY: 65216

African (AFR) AF: 0.326 AC: 12150 AN: 37250

American (AMR) AF: 0.179 AC: 2435 AN: 13640

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 707 AN: 3204

East Asian (EAS) AF: 0.463 AC: 2273 AN: 4906

South Asian (SAS) AF: 0.230 AC: 991 AN: 4300

European-Finnish (FIN) AF: 0.0836 AC: 595 AN: 7114

Middle Eastern (MID) AF: 0.267 AC: 71 AN: 266

European-Non Finnish (NFE) AF: 0.119 AC: 7389 AN: 62136

Other (OTH) AF: 0.209 AC: 390 AN: 1864

Alfa AF: 0.0382 Hom.: 21

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.59
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: rs200558502; hg19: chr7-93063701; COSMIC: COSV64008696;