rs35387386

Positions:

• chr3-122265173-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000388.4(CASR):​c.1377+2761C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 152,302 control chromosomes in the GnomAD database, including 52 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 0.021 (52 hom., cov: 32)
• Consequence: CASR NM_000388.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0208 (3165/152302) while in subpopulation NFE AF= 0.029 (1974/68022). AF 95% confidence interval is 0.028. There are 52 homozygotes in gnomad4. There are 1518 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASR	NM_000388.4	c.1377+2761C>T		intron_variant		ENST00000639785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASR	ENST00000639785.2	c.1377+2761C>T		intron_variant		1	NM_000388.4	P1
CASR	ENST00000498619.4	c.1377+2761C>T		intron_variant		1
CASR	ENST00000490131.7	c.1377+2761C>T		intron_variant		5
CASR	ENST00000638421.1	c.1377+2761C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3169 AN: 152184 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00533

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0369

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

GnomAD4 genome AF: 0.0208 AC: 3165 AN: 152302 Hom.: 52 Cov.: 32 AF XY: 0.0204 AC XY: 1518 AN XY: 74476

Gnomad4 AFR AF: 0.00534

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.0290

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0256 Hom.: 8

Bravo AF: 0.0201

Asia WGS AF: 0.00837 AC: 30 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	5.8
DANN	Benign	0.64

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: rs35387386; hg19: chr3-121984020;