rs2279802

Positions:

• chr3-122276094-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000388.4(CASR):​c.1608+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,218,580 control chromosomes in the GnomAD database, including 13,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1528 hom., cov: 32)
  • Exomes 𝑓: 0.11 (12450 hom.)
• Consequence: CASR NM_000388.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.644

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 3-122276094-G-A is Benign according to our data. Variant chr3-122276094-G-A is described in ClinVar as [Benign]. Clinvar id is 1261156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASR	NM_000388.4	c.1608+52G>A		intron_variant		ENST00000639785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASR	ENST00000639785.2	c.1608+52G>A		intron_variant		1	NM_000388.4	P1
CASR	ENST00000498619.4	c.1608+52G>A		intron_variant		1
CASR	ENST00000490131.7	c.1378-6019G>A		intron_variant		5
CASR	ENST00000638421.1	c.1608+52G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15298 AN: 152106 Hom.: 1519 Cov.: 32

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0943

GnomAD3 exomes AF: 0.156 AC: 37261 AN: 239278 Hom.: 5092 AF XY: 0.151 AC XY: 19615 AN XY: 130064

Gnomad AFR exome AF: 0.0427

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.0467

Gnomad EAS exome AF: 0.531

Gnomad SAS exome AF: 0.209

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0796

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.113 AC: 119967 AN: 1066354 Hom.: 12450 Cov.: 14 AF XY: 0.114 AC XY: 62615 AN XY: 547898

Gnomad4 AFR exome AF: 0.0387

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.0466

Gnomad4 EAS exome AF: 0.541

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.0785

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.101 AC: 15332 AN: 152226 Hom.: 1528 Cov.: 32 AF XY: 0.106 AC XY: 7909 AN XY: 74430

Gnomad4 AFR AF: 0.0421

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0521

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0817

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.0828 Hom.: 158

Bravo AF: 0.104

Asia WGS AF: 0.369 AC: 1278 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.0
DANN	Benign	0.65

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: rs2279802; hg19: chr3-121994941; COSMIC: COSV56141304;