3-122227252-A-G

Position:

• chr3-122227252-A-G

Variant summary

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

The ENST00000639785.2(CASR):​c.-242-26696A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 151,954 control chromosomes in the GnomAD database, including 41,679 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 0.74 (41679 hom., cov: 32)
• Consequence: CASR ENST00000639785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASR	NM_000388.4	c.-242-26696A>G		intron_variant		ENST00000639785.2	NP_000379.3
CASR	NM_001178065.2	c.-242-26696A>G		intron_variant			NP_001171536.2
CASR	XM_006713789.4	c.-242-26696A>G		intron_variant			XP_006713852.1
CASR	XM_047449065.1	c.-418-26696A>G		intron_variant			XP_047305021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASR	ENST00000639785.2	c.-242-26696A>G		intron_variant		1	NM_000388.4	ENSP00000491584	P1
CASR	ENST00000498619.4	c.-242-26696A>G		intron_variant		1		ENSP00000420194
CASR	ENST00000638421.1	c.-242-26696A>G		intron_variant		5		ENSP00000492190	P1
CASR	ENST00000643573.1	n.99-18126A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112206 AN: 151834 Hom.: 41647 Cov.: 32

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.739 AC: 112293 AN: 151954 Hom.: 41679 Cov.: 32 AF XY: 0.738 AC XY: 54827 AN XY: 74268

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.746

Alfa AF: 0.674 Hom.: 2192

Bravo AF: 0.750

Asia WGS AF: 0.540 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.15

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: rs7627468; hg19: chr3-121946099; COSMIC: COSV72229371;