Genetic Variant CALCR:c.1150-96delT (chr7-93434389-GA-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001742.4(CALCR):c.1150-96delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 492,956 control chromosomes in the GnomAD database, including 45 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 41 hom., cov: 0)

Exomes 𝑓: 0.076 ( 4 hom. )

Consequence

CALCR
NM_001742.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0166 (2253/135590) while in subpopulation AFR AF = 0.0485 (1809/37296). AF 95% confidence interval is 0.0466. There are 41 homozygotes in GnomAd4. There are 1101 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 41 Unknown gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2248

AN:

135550

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00558

Gnomad ASJ

AF:

0.00343

Gnomad EAS

AF:

0.000812

Gnomad SAS

AF:

0.000694

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.0105

Gnomad NFE

AF:

0.00343

Gnomad OTH

AF:

0.0173

GnomAD4 exome

AF:

0.0758

AC:

27085

AN:

357366

Hom.:

AF XY:

0.0766

AC XY:

14487

AN XY:

189010

show subpopulations

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

African (AFR)

AF:

0.0992

AC:

1032

AN:

10398

American (AMR)

AF:

0.0512

AC:

791

AN:

15444

Ashkenazi Jewish (ASJ)

AF:

0.0803

AC:

944

AN:

11760

East Asian (EAS)

AF:

0.00851

AC:

221

AN:

25956

South Asian (SAS)

AF:

0.0753

AC:

2153

AN:

28576

European-Finnish (FIN)

AF:

0.0817

AC:

2170

AN:

26568

Middle Eastern (MID)

AF:

0.0688

AC:

137

AN:

1992

European-Non Finnish (NFE)

AF:

0.0838

AC:

18103

AN:

215924

Other (OTH)

AF:

0.0739

AC:

1534

AN:

20748

⚠️ 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: 0.289

Heterozygous variant carriers

2301

4602

6902

9203

11504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0166

AC:

2253

AN:

135590

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1101

AN XY:

65236

show subpopulations

African (AFR)

AF:

0.0485

AC:

1809

AN:

37296

American (AMR)

AF:

0.00557

AC:

AN:

13644

Ashkenazi Jewish (ASJ)

AF:

0.00343

AC:

AN:

3204

East Asian (EAS)

AF:

0.000815

AC:

AN:

4908

South Asian (SAS)

AF:

0.000465

AC:

AN:

4302

European-Finnish (FIN)

AF:

0.0145

AC:

103

AN:

7114

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00343

AC:

213

AN:

62158

Other (OTH)

AF:

0.0171

AC:

AN:

1868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

104

208

311

415

519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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7-93434389-GAAAAA-GAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over