Genetic Variant CALCR:c.1150-99_1150-96dupTTTT (chr7-93434389-G-GAAAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001742.4(CALCR):c.1150-99_1150-96dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 507,760 control chromosomes in the GnomAD database, including 301 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.054 ( 278 hom., cov: 0)

Exomes 𝑓: 0.023 ( 23 hom. )

Consequence

CALCR
NM_001742.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.590

Publications

0 publications found

Variant links:

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)

CALCR links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 7-93434389-G-GAAAA is Benign according to our data. Variant chr7-93434389-G-GAAAA is described in ClinVar as [Benign]. Clinvar id is 1270922.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4 link	c.1150-99_1150-96dupTTTT	intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1	P30988-2
CALCR	NM_001164737.3 link	c.1198-99_1198-96dupTTTT	intron_variant	Intron 14 of 15		NP_001158209.2	P30988-1
CALCR	NM_001164738.2 link	c.1150-99_1150-96dupTTTT	intron_variant	Intron 11 of 12		NP_001158210.1	P30988-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7 link	c.1150-96_1150-95insTTTT		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1		P30988-2

Frequencies

GnomAD3 genomes

AF:

0.0541

AC:

7322

AN:

135332

Hom.:

278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0530

Gnomad AMI

AF:

0.0494

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.0463

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0731

Gnomad MID

AF:

0.0490

Gnomad NFE

AF:

0.0399

Gnomad OTH

AF:

0.0509

GnomAD4 exome

AF:

0.0227

AC:

8463

AN:

372386

Hom.:

AF XY:

0.0214

AC XY:

4226

AN XY:

197186

show subpopulations

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

African (AFR)

AF:

0.0271

AC:

292

AN:

10770

American (AMR)

AF:

0.0790

AC:

1216

AN:

15390

Ashkenazi Jewish (ASJ)

AF:

0.00875

AC:

109

AN:

12456

East Asian (EAS)

AF:

0.0332

AC:

859

AN:

25866

South Asian (SAS)

AF:

0.00887

AC:

260

AN:

29324

European-Finnish (FIN)

AF:

0.0392

AC:

1083

AN:

27610

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

2072

European-Non Finnish (NFE)

AF:

0.0180

AC:

4093

AN:

227316

Other (OTH)

AF:

0.0243

AC:

524

AN:

21582

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.335

Heterozygous variant carriers

525

1049

1574

2098

2623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0541

AC:

7327

AN:

135374

Hom.:

278

Cov.:

AF XY:

0.0561

AC XY:

3654

AN XY:

65124

show subpopulations

African (AFR)

AF:

0.0530

AC:

1971

AN:

37214

American (AMR)

AF:

0.133

AC:

1806

AN:

13568

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3204

East Asian (EAS)

AF:

0.0467

AC:

229

AN:

4904

South Asian (SAS)

AF:

0.0293

AC:

126

AN:

4296

European-Finnish (FIN)

AF:

0.0731

AC:

518

AN:

7090

Middle Eastern (MID)

AF:

0.0489

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0399

AC:

2479

AN:

62138

Other (OTH)

AF:

0.0504

AC:

AN:

1864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

275

550

825

1100

1375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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7-93434389-G-GAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over