Variant 5-96765340-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_001750.7(CAST):c.2037+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 74,254 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 81 hom. )

Failed GnomAD Quality Control

Consequence

CAST
NM_001750.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.966

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-96765340-A-G is Benign according to our data. Variant chr5-96765340-A-G is described in ClinVar as [Benign]. Clinvar id is 1631442.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00215 (160/74254) while in subpopulation SAS AF= 0.0294 (63/2142). AF 95% confidence interval is 0.0236. There are 1 homozygotes in gnomad4. There are 94 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAST	NM_001750.7 link	c.2037+15A>G		intron_variant		ENST00000675179.1	NP_001741.4	P20810-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000675179.1 link	c.2037+15A>G		intron_variant			NM_001750.7	ENSP00000501872.1		P20810-6

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

160

AN:

74204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00312

Gnomad ASJ

AF:

0.0192

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0225

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00209

GnomAD3 exomes

AF:

0.00132

AC:

189

AN:

143696

Hom.:

AF XY:

0.00154

AC XY:

126

AN XY:

81758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000880

Gnomad ASJ exome

AF:

0.00512

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00609

Gnomad FIN exome

AF:

0.000312

Gnomad NFE exome

AF:

0.000435

Gnomad OTH exome

AF:

0.00139

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00167

AC:

1616

AN:

969846

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

1072

AN XY:

500328

show subpopulations

Gnomad4 AFR exome

AF:

0.0000928

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00939

Gnomad4 EAS exome

AF:

0.0000843

Gnomad4 SAS exome

AF:

0.0126

Gnomad4 FIN exome

AF:

0.000360

Gnomad4 NFE exome

AF:

0.000567

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00215

AC:

160

AN:

74254

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

AN XY:

35170

show subpopulations

Gnomad4 AFR

AF:

0.000135

Gnomad4 AMR

AF:

0.00312

Gnomad4 ASJ

AF:

0.0192

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.00206

Alfa

AF:

0.000759

Hom.:

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

Labcorp Genetics (formerly Invitae), Labcorp

Oct 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.6

DANN

Benign

0.80

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