rs3749207

chr3-122261395-T-C

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.493-133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 814,398 control chromosomes in the GnomAD database, including 175,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (26636 hom., cov: 32)
  • Exomes 𝑓: 0.66 (149113 hom.)
• Consequence: CASR NM_000388.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.472

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=-0.88).
• BP6: Variant 3-122261395-T-C is Benign according to our data. Variant chr3-122261395-T-C is described in ClinVar as [Benign]. Clinvar id is 1268856.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-122261395-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASR	NM_000388.4	c.493-133T>C		intron_variant		ENST00000639785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASR	ENST00000639785.2	c.493-133T>C		intron_variant		1	NM_000388.4	P1
CASR	ENST00000498619.4	c.493-133T>C		intron_variant		1
CASR	ENST00000490131.7	c.493-133T>C		intron_variant		5
CASR	ENST00000638421.1	c.493-133T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85964 AN: 151934 Hom.: 26638 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.664 AC: 439915 AN: 662346 Hom.: 149113 AF XY: 0.673 AC XY: 241458 AN XY: 358764

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.574

Gnomad4 ASJ exome AF: 0.772

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.740

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.666

GnomAD4 genome AF: 0.566 AC: 85988 AN: 152052 Hom.: 26636 Cov.: 32 AF XY: 0.568 AC XY: 42201 AN XY: 74320

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.623

Alfa AF: 0.602 Hom.: 4107

Bravo AF: 0.547

Asia WGS AF: 0.613 AC: 2132 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	-0.88
Cadd	Benign	11
Dann	Benign	0.38

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: rs3749207; hg19: chr3-121980242;