7-93434594-G-GAA

Variant names:

• chr7-93434594-G-GAA
• rs74532696
• NM_001742.4:c.1150-302_1150-301dupTT

Variant summary

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

The NM_001742.4(CALCR):​c.1150-302_1150-301dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 146,826 control chromosomes in the GnomAD database, including 3,043 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3043 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-G-GAA is Benign according to our data. Variant chr7-93434594-G-GAA is described in ClinVar as [Benign]. Clinvar id is 1222864.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1150-302_1150-301dupTT		intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1198-302_1198-301dupTT		intron_variant	Intron 14 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.1150-302_1150-301dupTT		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.1150-301_1150-300insTT		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 28809 AN: 146766 Hom.: 3042 Cov.: 22

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.196 AC: 28822 AN: 146826 Hom.: 3043 Cov.: 22 AF XY: 0.202 AC XY: 14397 AN XY: 71388

African (AFR) AF: 0.136 AC: 5473 AN: 40120

American (AMR) AF: 0.280 AC: 4159 AN: 14830

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 536 AN: 3412

East Asian (EAS) AF: 0.389 AC: 1963 AN: 5046

South Asian (SAS) AF: 0.254 AC: 1180 AN: 4642

European-Finnish (FIN) AF: 0.223 AC: 2063 AN: 9256

Middle Eastern (MID) AF: 0.184 AC: 52 AN: 282

European-Non Finnish (NFE) AF: 0.194 AC: 12880 AN: 66350

Other (OTH) AF: 0.210 AC: 422 AN: 2006

Alfa AF: 0.0727 Hom.: 90

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		0.87
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: rs74532696; hg19: chr7-93063906; COSMIC: COSV64009865;