rs9875101

Positions:

• chr3-122249243-T-C

Variant summary

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

The NM_000388.4(CASR):​c.-242-4705T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,104 control chromosomes in the GnomAD database, including 34,272 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 0.67 (34272 hom., cov: 33)
• Consequence: CASR NM_000388.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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 = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASR	NM_000388.4	c.-242-4705T>C		intron_variant		ENST00000639785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASR	ENST00000639785.2	c.-242-4705T>C		intron_variant		1	NM_000388.4	P1
CASR	ENST00000498619.4	c.-242-4705T>C		intron_variant		1
CASR	ENST00000638421.1	c.-242-4705T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101582 AN: 151986 Hom.: 34256 Cov.: 33

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.668 AC: 101649 AN: 152104 Hom.: 34272 Cov.: 33 AF XY: 0.669 AC XY: 49774 AN XY: 74360

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.671

Alfa AF: 0.691 Hom.: 6028

Bravo AF: 0.676

Asia WGS AF: 0.494 AC: 1719 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.81

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: rs9875101; hg19: chr3-121968090;