3-122194523-G-T

Variant summary

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

The NM_000388.4(CASR):c.-243+10711G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,892 control chromosomes in the GnomAD database, including 3,927 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 0.20 (3927 hom., cov: 31)
• Consequence: CASR NM_000388.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASR	NM_000388.4	c.-243+10711G>T		intron_variant		ENST00000639785.2
CASR	NM_001178065.2	c.-243+9994G>T		intron_variant
CASR	XM_006713789.4	c.-243+9994G>T		intron_variant
CASR	XM_047449065.1	c.-419+9994G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASR	ENST00000639785.2	c.-243+10711G>T		intron_variant		1	NM_000388.4	P1
CASR	ENST00000498619.4	c.-243+9994G>T		intron_variant		1
CASR	ENST00000638421.1	c.-243+9994G>T		intron_variant		5		P1
CASR	ENST00000643573.1	n.98+9994G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30708 AN: 151774 Hom.: 3914 Cov.: 31

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.202 AC: 30741 AN: 151892 Hom.: 3927 Cov.: 31 AF XY: 0.208 AC XY: 15407 AN XY: 74246

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.207

Alfa AF: 0.215 Hom.: 3879

Bravo AF: 0.216

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.78
Dann	Benign	0.72

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: rs937627; hg19: chr3-121913370;