3-122258435-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000388.4(CASR):​c.492+1048G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 139,012 control chromosomes in the GnomAD database, including 7,364 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 0.31 ( 7364 hom., cov: 26)

Consequence

CASR
NM_000388.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0640
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CASRNM_000388.4 linkc.492+1048G>T intron_variant Intron 3 of 6 ENST00000639785.2 NP_000379.3 P41180-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CASRENST00000639785.2 linkc.492+1048G>T intron_variant Intron 3 of 6 1 NM_000388.4 ENSP00000491584.2 P41180-1
CASRENST00000498619.4 linkc.492+1048G>T intron_variant Intron 3 of 6 1 ENSP00000420194.1 P41180-2
CASRENST00000638421.1 linkc.492+1048G>T intron_variant Intron 3 of 6 5 ENSP00000492190.1 P41180-1
CASRENST00000490131.7 linkc.492+1048G>T intron_variant Intron 2 of 4 5 ENSP00000418685.2 A0A1X7SBX3

Frequencies

GnomAD3 genomes
AF:
0.310
AC:
43088
AN:
138928
Hom.:
7355
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.133
Gnomad AMI
AF:
0.167
Gnomad AMR
AF:
0.415
Gnomad ASJ
AF:
0.512
Gnomad EAS
AF:
0.556
Gnomad SAS
AF:
0.512
Gnomad FIN
AF:
0.362
Gnomad MID
AF:
0.519
Gnomad NFE
AF:
0.334
Gnomad OTH
AF:
0.363
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.310
AC:
43119
AN:
139012
Hom.:
7364
Cov.:
26
AF XY:
0.318
AC XY:
21309
AN XY:
66948
show subpopulations
Gnomad4 AFR
AF:
0.133
Gnomad4 AMR
AF:
0.415
Gnomad4 ASJ
AF:
0.512
Gnomad4 EAS
AF:
0.557
Gnomad4 SAS
AF:
0.514
Gnomad4 FIN
AF:
0.362
Gnomad4 NFE
AF:
0.334
Gnomad4 OTH
AF:
0.365
Alfa
AF:
0.326
Hom.:
11624
Bravo
AF:
0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
6.6
DANN
Benign
0.53

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.

Other links and lift over

dbSNP: rs10934578; hg19: chr3-121977282; COSMIC: COSV56141790; COSMIC: COSV56141790; API