rs6802749

Positions:

• chr3-122196010-G-A
• chr3-122196010-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+12198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,064 control chromosomes in the GnomAD database, including 2,407 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 0.17 (2407 hom., cov: 32)
• Consequence: CASR NM_000388.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASR	NM_000388.4	c.-243+12198G>A		intron_variant		ENST00000639785.2	NP_000379.3
CASR	NM_001178065.2	c.-243+11481G>A		intron_variant			NP_001171536.2
CASR	XM_006713789.4	c.-243+11481G>A		intron_variant			XP_006713852.1
CASR	XM_047449065.1	c.-419+11481G>A		intron_variant			XP_047305021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASR	ENST00000639785.2	c.-243+12198G>A		intron_variant		1	NM_000388.4	ENSP00000491584	P1
CASR	ENST00000498619.4	c.-243+11481G>A		intron_variant		1		ENSP00000420194
CASR	ENST00000638421.1	c.-243+11481G>A		intron_variant		5		ENSP00000492190	P1
CASR	ENST00000643573.1	n.98+11481G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26581 AN: 151946 Hom.: 2400 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.175 AC: 26594 AN: 152064 Hom.: 2407 Cov.: 32 AF XY: 0.170 AC XY: 12664 AN XY: 74336

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0303

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.167

Alfa AF: 0.153 Hom.: 926

Bravo AF: 0.171

Asia WGS AF: 0.0800 AC: 280 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.76

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: rs6802749; hg19: chr3-121914857;