dbSNP rs3749207: CASR:c.493-133T>C (chr3-122261395-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000388.4(CASR):c.493-133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 814,398 control chromosomes in the GnomAD database, including 175,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 26636 hom., cov: 32)

Exomes 𝑓: 0.66 ( 149113 hom. )

Consequence

CASR
NM_000388.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.472

Variant links:

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]

CASR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-122261395-T-C is Benign according to our data. Variant chr3-122261395-T-C is described in ClinVar as [Benign]. Clinvar id is 1268856.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-122261395-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASR	NM_000388.4 link	c.493-133T>C		intron_variant	Intron 3 of 6	ENST00000639785.2	NP_000379.3	P41180-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CASR	ENST00000639785.2 link	c.493-133T>C	intron_variant	Intron 3 of 6	1	NM_000388.4	ENSP00000491584.2	P41180-1
CASR	ENST00000498619.4 link	c.493-133T>C	intron_variant	Intron 3 of 6	1		ENSP00000420194.1	P41180-2
CASR	ENST00000638421.1 link	c.493-133T>C	intron_variant	Intron 3 of 6	5		ENSP00000492190.1	P41180-1
CASR	ENST00000490131.7 link	c.493-133T>C	intron_variant	Intron 2 of 4	5		ENSP00000418685.2	A0A1X7SBX3

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

85964

AN:

151934

Hom.:

26638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.606

Gnomad ASJ

AF:

0.775

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.625

GnomAD4 exome

AF:

0.664

AC:

439915

AN:

662346

Hom.:

149113

AF XY:

0.673

AC XY:

241458

AN XY:

358764

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.574

Gnomad4 ASJ exome

AF:

0.772

Gnomad4 EAS exome

AF:

0.565

Gnomad4 SAS exome

AF:

0.740

Gnomad4 FIN exome

AF:

0.676

Gnomad4 NFE exome

AF:

0.679

Gnomad4 OTH exome

AF:

0.666

GnomAD4 genome

AF:

0.566

AC:

85988

AN:

152052

Hom.:

26636

Cov.:

AF XY:

0.568

AC XY:

42201

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.606

Gnomad4 ASJ

AF:

0.775

Gnomad4 EAS

AF:

0.555

Gnomad4 SAS

AF:

0.724

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.623

Alfa

AF:

0.602

Hom.:

4107

Bravo

AF:

0.547

Asia WGS

AF:

0.613

AC:

2132

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over