dbSNP rs10488551: CALCR:c.-27+39882G>A (chr7-93534407-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001742.4(CALCR):c.-27+39882G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,578 control chromosomes in the GnomAD database, including 7,174 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7174 hom., cov: 31)

Consequence

CALCR
NM_001742.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0540

Publications

5 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:

LOC105375400 (HGNC:):

LOC105375400 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALCR	NM_001742.4	MANE Select	c.-27+39882G>A	intron	N/A	NP_001733.1	P30988-2
CALCR	NM_001164737.3		c.-97-38433G>A	intron	N/A	NP_001158209.2	A0A0A0MSQ7
CALCR	NM_001164738.2		c.-27+25114G>A	intron	N/A	NP_001158210.1	P30988-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALCR	ENST00000426151.7	TSL:1 MANE Select	c.-27+39882G>A	intron	N/A	ENSP00000389295.1	P30988-2
CALCR	ENST00000394441.5	TSL:1	c.-27+25114G>A	intron	N/A	ENSP00000377959.1	P30988-2
CALCR	ENST00000649521.1		c.-97-38433G>A	intron	N/A	ENSP00000497687.1	P30988-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42755

AN:

151460

Hom.:

7175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0936

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.305

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

GnomAD4 genome

AF:

0.282

AC:

42751

AN:

151578

Hom.:

7174

Cov.:

AF XY:

0.282

AC XY:

20907

AN XY:

74084

show subpopulations

African (AFR)

AF:

0.0935

AC:

3879

AN:

41468

American (AMR)

AF:

0.264

AC:

4003

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

1295

AN:

3454

East Asian (EAS)

AF:

0.302

AC:

1557

AN:

5164

South Asian (SAS)

AF:

0.383

AC:

1846

AN:

4814

European-Finnish (FIN)

AF:

0.331

AC:

3501

AN:

10566

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.377

AC:

25503

AN:

67632

Other (OTH)

AF:

0.308

AC:

647

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1447

2894

4340

5787

7234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.345

Hom.:

28711

Bravo

AF:

0.266

Asia WGS

AF:

0.277

AC:

966

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

(source)

DANN

Benign

0.74

PhyloP100

-0.054

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over