Genetic Variant NM_001742.4:c.51+1879A>C (chr7-93485052-T-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.51+1879A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,644 control chromosomes in the GnomAD database, including 21,565 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 0.53 ( 21565 hom., cov: 33)

Consequence

CALCR
NM_001742.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.304

Publications

3 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:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 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.51+1879A>C	intron	N/A	NP_001733.1	P30988-2
CALCR	NM_001164737.3		c.51+1879A>C	intron	N/A	NP_001158209.2	A0A0A0MSQ7
CALCR	NM_001164738.2		c.51+1879A>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.51+1879A>C	intron	N/A	ENSP00000389295.1	P30988-2
CALCR	ENST00000394441.5	TSL:1	c.51+1879A>C	intron	N/A	ENSP00000377959.1	P30988-2
CALCR	ENST00000415529.2	TSL:1	n.51+1879A>C	intron	N/A	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80230

AN:

151526

Hom.:

21542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.609

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.692

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.530

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

GnomAD4 genome

AF:

0.529

AC:

80295

AN:

151644

Hom.:

21565

Cov.:

AF XY:

0.526

AC XY:

38955

AN XY:

74086

show subpopulations

African (AFR)

AF:

0.609

AC:

25232

AN:

41436

American (AMR)

AF:

0.437

AC:

6642

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1831

AN:

3468

East Asian (EAS)

AF:

0.692

AC:

3535

AN:

5106

South Asian (SAS)

AF:

0.581

AC:

2799

AN:

4820

European-Finnish (FIN)

AF:

0.453

AC:

4790

AN:

10578

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.497

AC:

33679

AN:

67728

Other (OTH)

AF:

0.534

AC:

1126

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1965

3930

5895

7860

9825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.516

Hom.:

2627

Bravo

AF:

0.528

Asia WGS

AF:

0.607

AC:

2110

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.4

(source)

DANN

Benign

0.31

PhyloP100

0.30

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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