Genetic Variant NM_001742.4:c.-26-14678T>C (chr7-93501685-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001742.4(CALCR):c.-26-14678T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,050 control chromosomes in the GnomAD database, including 2,648 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 0.13 ( 2648 hom., cov: 32)

Consequence

CALCR
NM_001742.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.895

Publications

1 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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new If you want to explore the variant's impact on the transcript NM_001742.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 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.-26-14678T>C	intron	N/A	NP_001733.1	P30988-2
CALCR	NM_001164737.3		c.-97-5711T>C	intron	N/A	NP_001158209.2	A0A0A0MSQ7
CALCR	NM_001164738.2		c.-26-14678T>C	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.-26-14678T>C	intron	N/A	ENSP00000389295.1	P30988-2
CALCR	ENST00000394441.5	TSL:1	c.-26-14678T>C	intron	N/A	ENSP00000377959.1	P30988-2
CALCR	ENST00000649521.1		c.-97-5711T>C	intron	N/A	ENSP00000497687.1	P30988-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19195

AN:

151932

Hom.:

2634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.0969

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0167

Gnomad OTH

AF:

0.111

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

GnomAD4 genome

AF:

0.127

AC:

19242

AN:

152050

Hom.:

2648

Cov.:

AF XY:

0.128

AC XY:

9502

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.330

AC:

13658

AN:

41442

American (AMR)

AF:

0.106

AC:

1611

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

121

AN:

3472

East Asian (EAS)

AF:

0.286

AC:

1473

AN:

5142

South Asian (SAS)

AF:

0.0960

AC:

462

AN:

4814

European-Finnish (FIN)

AF:

0.0477

AC:

506

AN:

10610

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0167

AC:

1138

AN:

67996

Other (OTH)

AF:

0.111

AC:

234

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

720

1440

2161

2881

3601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.0849

Hom.:

419

Bravo

AF:

0.139

Asia WGS

AF:

0.223

AC:

774

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.1

(source)

DANN

Benign

0.30

PhyloP100

-0.90

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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