3-122184060-T-C

Position:

• chr3-122184060-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000639785.2(CASR):​c.-243+248T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,026 control chromosomes in the GnomAD database, including 3,859 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 0.20 (3859 hom., cov: 32)
• Consequence: CASR ENST00000639785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASR	NM_000388.4	c.-243+248T>C		intron_variant		ENST00000639785.2	NP_000379.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASR	ENST00000639785.2	c.-243+248T>C		intron_variant		1	NM_000388.4	ENSP00000491584	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29767 AN: 151908 Hom.: 3847 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29786 AN: 152026 Hom.: 3859 Cov.: 32 AF XY: 0.201 AC XY: 14955 AN XY: 74326

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.203

Alfa AF: 0.215 Hom.: 5393

Bravo AF: 0.208

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs1048213; hg19: chr3-121902907;