rs3749204

Variant names:

• chr3-122257685-A-C
• rs3749204
• NM_000388.4:c.492+298A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-122257685-A-C
• chr3-122257685-A-G
• chr3-122257685-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000388.4(CASR):​c.492+298A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASR NM_000388.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASR	NM_000388.4	c.492+298A>C		intron_variant	Intron 3 of 6	ENST00000639785.2	NP_000379.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASR	ENST00000639785.2	c.492+298A>C		intron_variant	Intron 3 of 6	1	NM_000388.4	ENSP00000491584.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 127224 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65054

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 4286

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 5868

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 4426

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 9136

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 9132

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 6434

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 79442

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 7906

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3749204; hg19: chr3-121976532;