Variant chr3-122282024-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000388.4(CASR):c.1609-89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,586,760 control chromosomes in the GnomAD database, including 348,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 26503 hom., cov: 32)

Exomes 𝑓: 0.67 ( 322066 hom. )

Consequence

CASR
NM_000388.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.368

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-122282024-C-T is Benign according to our data. Variant chr3-122282024-C-T is described in ClinVar as [Benign]. Clinvar id is 1192651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-122282024-C-T 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/exons	MANE	UniProt
CASR	NM_000388.4 linkuse as main transcript	c.1609-89C>T		intron_variant		ENST00000639785.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
CASR	ENST00000639785.2 linkuse as main transcript	c.1609-89C>T	intron_variant	1	NM_000388.4	P1	P41180-1
CASR	ENST00000498619.4 linkuse as main transcript	c.1609-59C>T	intron_variant	1			P41180-2
CASR	ENST00000490131.7 linkuse as main transcript	c.1378-89C>T	intron_variant	5
CASR	ENST00000638421.1 linkuse as main transcript	c.1609-89C>T	intron_variant	5		P1	P41180-1

Frequencies

GnomAD3 genomes

AF:

0.563

AC:

85609

AN:

151978

Hom.:

26505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.775

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.625

GnomAD4 exome

AF:

0.665

AC:

954660

AN:

1434662

Hom.:

322066

AF XY:

0.671

AC XY:

477952

AN XY:

712644

show subpopulations

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.572

Gnomad4 ASJ exome

AF:

0.773

Gnomad4 EAS exome

AF:

0.566

Gnomad4 SAS exome

AF:

0.739

Gnomad4 FIN exome

AF:

0.679

Gnomad4 NFE exome

AF:

0.675

Gnomad4 OTH exome

AF:

0.668

GnomAD4 genome

AF:

0.563

AC:

85631

AN:

152098

Hom.:

26503

Cov.:

AF XY:

0.566

AC XY:

42040

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.605

Gnomad4 ASJ

AF:

0.775

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.724

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.623

Alfa

AF:

0.606

Hom.:

5828

Bravo

AF:

0.544

Asia WGS

AF:

0.611

AC:

2124

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Autosomal dominant hypocalcemia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Familial hypocalciuric hypercalcemia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Neonatal severe primary hyperparathyroidism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.9

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

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