Genetic Variant NM_001742.4:c.1149+149C>G (chr7-93435803-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001742.4(CALCR):c.1149+149C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 232,476 control chromosomes in the GnomAD database, including 46,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 29398 hom., cov: 26)

Exomes 𝑓: 0.62 ( 16835 hom. )

Consequence

CALCR
NM_001742.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.769

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 7-93435803-G-C is Benign according to our data. Variant chr7-93435803-G-C is described in ClinVar as [Benign]. Clinvar id is 1237362.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4 link	c.1149+149C>G	intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1	P30988-2
CALCR	NM_001164737.3 link	c.1197+149C>G	intron_variant	Intron 14 of 15		NP_001158209.2	P30988-1
CALCR	NM_001164738.2 link	c.1149+149C>G	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.1149+149C>G		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1		P30988-2

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

92677

AN:

148452

Hom.:

29391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.699

Gnomad EAS

AF:

0.883

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.701

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.666

GnomAD4 exome

AF:

0.619

AC:

51959

AN:

83920

Hom.:

16835

AF XY:

0.619

AC XY:

29007

AN XY:

46862

show subpopulations

African (AFR)

AF:

0.570

AC:

1353

AN:

2372

American (AMR)

AF:

0.747

AC:

1926

AN:

2580

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

1741

AN:

2622

East Asian (EAS)

AF:

0.903

AC:

5721

AN:

6336

South Asian (SAS)

AF:

0.646

AC:

665

AN:

1030

European-Finnish (FIN)

AF:

0.442

AC:

2017

AN:

4562

Middle Eastern (MID)

AF:

0.705

AC:

265

AN:

376

European-Non Finnish (NFE)

AF:

0.593

AC:

35217

AN:

59350

Other (OTH)

AF:

0.651

AC:

3054

AN:

4692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

885

1770

2655

3540

4425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.624

AC:

92730

AN:

148556

Hom.:

29398

Cov.:

AF XY:

0.624

AC XY:

45109

AN XY:

72334

show subpopulations

African (AFR)

AF:

0.598

AC:

24167

AN:

40414

American (AMR)

AF:

0.732

AC:

10896

AN:

14892

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

2411

AN:

3450

East Asian (EAS)

AF:

0.883

AC:

4522

AN:

5122

South Asian (SAS)

AF:

0.655

AC:

3086

AN:

4710

European-Finnish (FIN)

AF:

0.491

AC:

4702

AN:

9572

Middle Eastern (MID)

AF:

0.709

AC:

207

AN:

292

European-Non Finnish (NFE)

AF:

0.609

AC:

40906

AN:

67160

Other (OTH)

AF:

0.667

AC:

1371

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1465

2931

4396

5862

7327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.435

Hom.:

1076

Bravo

AF:

0.646

Asia WGS

AF:

0.780

AC:

2708

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.85

(source)

DANN

Benign

0.20

PhyloP100

-0.77

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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NM_001742.4:c.1149+149C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over