rs1965357

Positions:

• chr3-122249705-C-T

Variant summary

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

The ENST00000639785.2(CASR):​c.-242-4243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,280 control chromosomes in the GnomAD database, including 53,721 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 0.84 (53721 hom., cov: 34)
• Consequence: CASR ENST00000639785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASR	NM_000388.4	c.-242-4243C>T		intron_variant		ENST00000639785.2	NP_000379.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASR	ENST00000639785.2	c.-242-4243C>T		intron_variant		1	NM_000388.4	ENSP00000491584	P1
CASR	ENST00000498619.4	c.-242-4243C>T		intron_variant		1		ENSP00000420194
CASR	ENST00000638421.1	c.-242-4243C>T		intron_variant		5		ENSP00000492190	P1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127319 AN: 152162 Hom.: 53695 Cov.: 34

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.839

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

GnomAD4 genome AF: 0.837 AC: 127398 AN: 152280 Hom.: 53721 Cov.: 34 AF XY: 0.836 AC XY: 62239 AN XY: 74472

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.830

Alfa AF: 0.856 Hom.: 7726

Bravo AF: 0.835

Asia WGS AF: 0.587 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.41

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: rs1965357; hg19: chr3-121968552;