Genetic Variant CALCR:c.1150-97_1150-96dupTT (chr7-93434389-G-GAA) – 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.1150-97_1150-96dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 502,452 control chromosomes in the GnomAD database, including 2,348 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 1990 hom., cov: 0)

Exomes 𝑓: 0.14 ( 358 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-GAA is Benign according to our data. Variant chr7-93434389-G-GAA is described in ClinVar as [Benign]. Clinvar id is 1274232.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4 link	c.1150-97_1150-96dupTT	intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1	P30988-2
CALCR	NM_001164737.3 link	c.1198-97_1198-96dupTT	intron_variant	Intron 14 of 15		NP_001158209.2	P30988-1
CALCR	NM_001164738.2 link	c.1150-97_1150-96dupTT	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_1150-95insTT		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1		P30988-2

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

22049

AN:

135296

Hom.:

1985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0708

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.168

GnomAD4 exome

AF:

0.145

AC:

53079

AN:

367116

Hom.:

358

AF XY:

0.145

AC XY:

28131

AN XY:

194376

show subpopulations

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

African (AFR)

AF:

0.0690

AC:

735

AN:

10656

American (AMR)

AF:

0.164

AC:

2525

AN:

15440

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

1415

AN:

12206

East Asian (EAS)

AF:

0.293

AC:

7434

AN:

25370

South Asian (SAS)

AF:

0.150

AC:

4297

AN:

28666

European-Finnish (FIN)

AF:

0.139

AC:

3812

AN:

27444

Middle Eastern (MID)

AF:

0.123

AC:

253

AN:

2056

European-Non Finnish (NFE)

AF:

0.132

AC:

29621

AN:

223994

Other (OTH)

AF:

0.140

AC:

2987

AN:

21284

⚠️ 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: 0.385

Heterozygous variant carriers

2346

4692

7039

9385

11731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.163

AC:

22052

AN:

135336

Hom.:

1990

Cov.:

AF XY:

0.166

AC XY:

10833

AN XY:

65102

show subpopulations

African (AFR)

AF:

0.0708

AC:

2637

AN:

37262

American (AMR)

AF:

0.196

AC:

2669

AN:

13624

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

506

AN:

3192

East Asian (EAS)

AF:

0.337

AC:

1650

AN:

4890

South Asian (SAS)

AF:

0.232

AC:

995

AN:

4286

European-Finnish (FIN)

AF:

0.192

AC:

1357

AN:

7082

Middle Eastern (MID)

AF:

0.143

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.190

AC:

11798

AN:

62044

Other (OTH)

AF:

0.169

AC:

315

AN:

1860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

769

1539

2308

3078

3847

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 18, 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 (auto)

(source)

Splicing

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

Publications

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7-93434389-G-GAA

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