Genetic Variant CALCR:c.1150-98_1150-96dupTTT (chr7-93434389-G-GAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001742.4(CALCR):c.1150-98_1150-96dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 508,740 control chromosomes in the GnomAD database, including 15 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0047 ( 9 hom., cov: 0)

Exomes 𝑓: 0.012 ( 6 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 9 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4 link	c.1150-98_1150-96dupTTT	intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1	P30988-2
CALCR	NM_001164737.3 link	c.1198-98_1198-96dupTTT	intron_variant	Intron 14 of 15		NP_001158209.2	P30988-1
CALCR	NM_001164738.2 link	c.1150-98_1150-96dupTTT	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_1150-95insTTT		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1		P30988-2

Frequencies

GnomAD3 genomes

AF:

0.00468

AC:

635

AN:

135600

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00228

Gnomad ASJ

AF:

0.000312

Gnomad EAS

AF:

0.000812

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000281

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000273

Gnomad OTH

AF:

0.00378

GnomAD4 exome

AF:

0.0123

AC:

4606

AN:

373100

Hom.:

AF XY:

0.0119

AC XY:

2344

AN XY:

197516

show subpopulations

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

African (AFR)

AF:

0.0183

AC:

197

AN:

10778

American (AMR)

AF:

0.0326

AC:

510

AN:

15632

Ashkenazi Jewish (ASJ)

AF:

0.00732

AC:

AN:

12430

East Asian (EAS)

AF:

0.0261

AC:

674

AN:

25844

South Asian (SAS)

AF:

0.0143

AC:

416

AN:

29158

European-Finnish (FIN)

AF:

0.0122

AC:

341

AN:

27864

Middle Eastern (MID)

AF:

0.00627

AC:

AN:

2074

European-Non Finnish (NFE)

AF:

0.00930

AC:

2117

AN:

227656

Other (OTH)

AF:

0.0114

AC:

247

AN:

21664

⚠️ 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: 0.306

Heterozygous variant carriers

338

676

1015

1353

1691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00468

AC:

635

AN:

135640

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

303

AN XY:

65272

show subpopulations

African (AFR)

AF:

0.0154

AC:

573

AN:

37294

American (AMR)

AF:

0.00227

AC:

AN:

13644

Ashkenazi Jewish (ASJ)

AF:

0.000312

AC:

AN:

3202

East Asian (EAS)

AF:

0.000815

AC:

AN:

4908

South Asian (SAS)

AF:

0.00

AC:

AN:

4302

European-Finnish (FIN)

AF:

0.000281

AC:

AN:

7130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.000273

AC:

AN:

62196

Other (OTH)

AF:

0.00375

AC:

AN:

1868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

102

127

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

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

Publications

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7-93434389-GAAAAA-GAAAAAAAA

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