rs17251221

Positions:

• chr3-122274400-A-G

Variant summary

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

The ENST00000639785.2(CASR):​c.1378-1412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,334 control chromosomes in the GnomAD database, including 1,226 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 0.11 (1226 hom., cov: 32)
• Consequence: CASR ENST00000639785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASR	NM_000388.4	c.1378-1412A>G		intron_variant		ENST00000639785.2	NP_000379.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASR	ENST00000639785.2	c.1378-1412A>G		intron_variant		1	NM_000388.4	ENSP00000491584	P1
CASR	ENST00000498619.4	c.1378-1412A>G		intron_variant		1		ENSP00000420194
CASR	ENST00000490131.7	c.1378-7713A>G		intron_variant		5		ENSP00000418685
CASR	ENST00000638421.1	c.1378-1412A>G		intron_variant		5		ENSP00000492190	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16789 AN: 152216 Hom.: 1225 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.110 AC: 16787 AN: 152334 Hom.: 1226 Cov.: 32 AF XY: 0.111 AC XY: 8301 AN XY: 74498

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0316

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.142

Alfa AF: 0.143 Hom.: 1948

Bravo AF: 0.105

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.80

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: rs17251221; hg19: chr3-121993247;