Variant rs3214019 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001750.7(CAST):c.2131-32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 1,581,824 control chromosomes in the GnomAD database, including 5,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.096 ( 850 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4990 hom. )

Consequence

CAST
NM_001750.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68

Variant links:

Genes affected

CAST (HGNC:1515): (calpastatin) The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1-4), and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

CAST links:

ERAP1 (HGNC:18173): (endoplasmic reticulum aminopeptidase 1) The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

ERAP1 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=-0.91).

BP6

Variant 5-96767406-A-G is Benign according to our data. Variant chr5-96767406-A-G is described in ClinVar as [Benign]. Clinvar id is 1286868.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7 linkuse as main transcript	c.2131-32A>G		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1 linkuse as main transcript	c.2131-32A>G		intron_variant			NM_001750.7	A2	P20810-6

Frequencies

GnomAD3 genomes

AF:

0.0962

AC:

14633

AN:

152158

Hom.:

851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.0711

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0409

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0788

AC:

19699

AN:

250078

Hom.:

1018

AF XY:

0.0812

AC XY:

10979

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0508

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0144

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.0424

Gnomad NFE exome

AF:

0.0721

Gnomad OTH exome

AF:

0.0891

GnomAD4 exome

AF:

0.0780

AC:

111451

AN:

1429548

Hom.:

4990

Cov.:

AF XY:

0.0799

AC XY:

57009

AN XY:

713530

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.0531

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.0418

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.0435

Gnomad4 NFE exome

AF:

0.0726

Gnomad4 OTH exome

AF:

0.0884

GnomAD4 genome

AF:

0.0962

AC:

14643

AN:

152276

Hom.:

850

Cov.:

AF XY:

0.0960

AC XY:

7152

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0709

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.0264

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.0409

Gnomad4 NFE

AF:

0.0734

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0979

Hom.:

207

Bravo

AF:

0.0999

Asia WGS

AF:

0.0880

AC:

305

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.22

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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