GeneBe

3-122194523-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000388.4(CASR):​c.-243+10711G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Consequence

CASR
NM_000388.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.272

Publications

4 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CASRNM_000388.4 linkc.-243+10711G>A intron_variant Intron 1 of 6 ENST00000639785.2 NP_000379.3 P41180-1
CASRNM_001178065.2 linkc.-243+9994G>A intron_variant Intron 1 of 6 NP_001171536.2 P41180-2
CASRXM_006713789.4 linkc.-243+9994G>A intron_variant Intron 1 of 6 XP_006713852.1 P41180-1
CASRXM_047449065.1 linkc.-419+9994G>A intron_variant Intron 1 of 5 XP_047305021.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CASRENST00000639785.2 linkc.-243+10711G>A intron_variant Intron 1 of 6 1 NM_000388.4 ENSP00000491584.2 P41180-1
CASRENST00000498619.4 linkc.-243+9994G>A intron_variant Intron 1 of 6 1 ENSP00000420194.1 P41180-2
CASRENST00000638421.1 linkc.-243+9994G>A intron_variant Intron 1 of 6 5 ENSP00000492190.1 P41180-1
CASRENST00000643573.1 linkn.98+9994G>A intron_variant Intron 1 of 2

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151840
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151840
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74156
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41322
American (AMR)
AF:
0.00
AC:
0
AN:
15252
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3460
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5158
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4812
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10556
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67964
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
5154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.95
DANN
Benign
0.63
PhyloP100
-0.27

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

Other links and lift over

dbSNP: rs937627; hg19: chr3-121913370; API