7-93434594-GA-G

Variant names:

• chr7-93434594-GA-G
• rs74532696
• NM_001742.4:c.1150-301delT

Variant summary

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

The NM_001742.4(CALCR):​c.1150-301delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 146,998 control chromosomes in the GnomAD database, including 92 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.020 (92 hom., cov: 22)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.868
• 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 7-93434594-GA-G is Benign according to our data. Variant chr7-93434594-GA-G is described in ClinVar as [Benign]. Clinvar id is 1261013.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1150-301delT		intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1198-301delT		intron_variant	Intron 14 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.1150-301delT		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.1150-301delT		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 2927 AN: 146938 Hom.: 92 Cov.: 22

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00775

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0261

Gnomad NFE AF: 0.000873

Gnomad OTH AF: 0.0150

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

GnomAD4 genome AF: 0.0200 AC: 2934 AN: 146998 Hom.: 92 Cov.: 22 AF XY: 0.0185 AC XY: 1322 AN XY: 71488

African (AFR) AF: 0.0678 AC: 2723 AN: 40146

American (AMR) AF: 0.00774 AC: 115 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5054

South Asian (SAS) AF: 0.00 AC: 0 AN: 4648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9302

Middle Eastern (MID) AF: 0.0284 AC: 8 AN: 282

European-Non Finnish (NFE) AF: 0.000873 AC: 58 AN: 66402

Other (OTH) AF: 0.0149 AC: 30 AN: 2014

Alfa AF: 0.00 Hom.: 90

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 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		0.87
Mutation Taster		=100/0	polymorphism

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: rs74532696; hg19: chr7-93063906;