Variant rs2279802 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CASR	NM_000388.4 linkuse as main transcript	c.1608+52G>A		intron_variant		ENST00000639785.2	NP_000379.3	P41180-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CASR	ENST00000639785.2 linkuse as main transcript	c.1608+52G>A	intron_variant	1	NM_000388.4	ENSP00000491584.2	P41180-1
CASR	ENST00000498619.4 linkuse as main transcript	c.1608+52G>A	intron_variant	1		ENSP00000420194.1	P41180-2
CASR	ENST00000638421.1 linkuse as main transcript	c.1608+52G>A	intron_variant	5		ENSP00000492190.1	P41180-1
CASR	ENST00000490131.7 linkuse as main transcript	c.1378-6019G>A	intron_variant	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

GnomAD3 exomes

AF:

0.156

AC:

37261

AN:

239278

Hom.:

5092

AF XY:

0.151

AC XY:

19615

AN XY:

130064

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 SAS exome

AF:

0.209

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

Gnomad4 AFR exome

AF:

0.0387

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.0466

Gnomad4 EAS exome

AF:

0.541

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.0785

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.101

AC:

15332

AN:

152226

Hom.:

1528

Cov.:

AF XY:

0.106

AC XY:

7909

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0421

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0817

Gnomad4 OTH

AF:

0.0990

Alfa

AF:

0.0828

Hom.:

158

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.0

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over