rs2279802

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000388.4(CASR):c.1608+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,218,580 control chromosomes in the GnomAD database, including 13,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1528 hom., cov: 32)

Exomes 𝑓: 0.11 ( 12450 hom. )

Consequence

CASR
NM_000388.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.644

Publications

5 publications found

Variant links:

Genes affected

CASR (HGNC:1514): (calcium sensing receptor) The protein encoded by this gene is a plasma membrane G protein-coupled receptor that senses small changes in circulating calcium concentration. The encoded protein couples this information to intracellular signaling pathways that modify parathyroid hormone secretion or renal cation handling, and thus this protein plays an essential role in maintaining mineral ion homeostasis. Mutations in this gene are a cause of familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. [provided by RefSeq, Aug 2017]

CASR Gene-Disease associations (from GenCC):

autosomal dominant hypocalcemia 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, ClinGen, Labcorp Genetics (formerly Invitae)
familial hypocalciuric hypercalcemia 1
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Illumina, Orphanet, Genomics England PanelApp
neonatal severe primary hyperparathyroidism
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
autosomal dominant hypocalcemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy, idiopathic generalized, susceptibility to, 8
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CASR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-122276094-G-A is Benign according to our data. Variant chr3-122276094-G-A is described in ClinVar as Benign. ClinVar VariationId is 1261156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASR	NM_000388.4 link	c.1608+52G>A		intron_variant	Intron 5 of 6	ENST00000639785.2	NP_000379.3	P41180-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CASR	ENST00000639785.2 link	c.1608+52G>A	intron_variant	Intron 5 of 6	1	NM_000388.4	ENSP00000491584.2	P41180-1
CASR	ENST00000498619.4 link	c.1608+52G>A	intron_variant	Intron 5 of 6	1		ENSP00000420194.1	P41180-2
CASR	ENST00000638421.1 link	c.1608+52G>A	intron_variant	Intron 5 of 6	5		ENSP00000492190.1	P41180-1
CASR	ENST00000490131.7 link	c.1378-6019G>A	intron_variant	Intron 3 of 4	5		ENSP00000418685.2	A0A1X7SBX3

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15298

AN:

152106

Hom.:

1519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0421

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0817

Gnomad OTH

AF:

0.0943

GnomAD2 exomes

AF:

0.156

AC:

37261

AN:

239278

AF XY:

0.151

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.0467

Gnomad EAS exome

AF:

0.531

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0796

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.113

AC:

119967

AN:

1066354

Hom.:

12450

Cov.:

AF XY:

0.114

AC XY:

62615

AN XY:

547898

show subpopulations

African (AFR)

AF:

0.0387

AC:

1001

AN:

25872

American (AMR)

AF:

0.259

AC:

11270

AN:

43454

Ashkenazi Jewish (ASJ)

AF:

0.0466

AC:

1105

AN:

23688

East Asian (EAS)

AF:

0.541

AC:

20388

AN:

37672

South Asian (SAS)

AF:

0.201

AC:

15581

AN:

77620

European-Finnish (FIN)

AF:

0.106

AC:

5621

AN:

52964

Middle Eastern (MID)

AF:

0.0388

AC:

189

AN:

4868

European-Non Finnish (NFE)

AF:

0.0785

AC:

59101

AN:

752862

Other (OTH)

AF:

0.121

AC:

5711

AN:

47354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5372

10744

16116

21488

26860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2070

4140

6210

8280

10350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15332

AN:

152226

Hom.:

1528

Cov.:

AF XY:

0.106

AC XY:

7909

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0421

AC:

1749

AN:

41558

American (AMR)

AF:

0.179

AC:

2734

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0521

AC:

181

AN:

3472

East Asian (EAS)

AF:

0.521

AC:

2687

AN:

5156

South Asian (SAS)

AF:

0.233

AC:

1125

AN:

4822

European-Finnish (FIN)

AF:

0.101

AC:

1072

AN:

10610

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0817

AC:

5556

AN:

67988

Other (OTH)

AF:

0.0990

AC:

209

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

640

1280

1920

2560

3200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0817

Hom.:

159

Bravo

AF:

0.104

Asia WGS

AF:

0.369

AC:

1278

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

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

-0.75

CADD

Benign

9.0

(source)

DANN

Benign

0.65

PhyloP100

0.64

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over