5-96765362-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001750.7(CAST):c.2037+38dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (48100 hom., cov: 0)
  • Exomes 𝑓: 0.81 (210039 hom.)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-96765362-T-TA is Benign according to our data. Variant chr5-96765362-T-TA is described in ClinVar as [Benign]. Clinvar id is 1248298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.2037+38dup		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.2037+38dup		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.823 AC: 115839 AN: 140774 Hom.: 48080 Cov.: 0

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.819

GnomAD3 exomes AF: 0.812 AC: 48622 AN: 59914 Hom.: 21585 AF XY: 0.813 AC XY: 27240 AN XY: 33524

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.899

Gnomad ASJ exome AF: 0.828

Gnomad EAS exome AF: 0.328

Gnomad SAS exome AF: 0.795

Gnomad FIN exome AF: 0.855

Gnomad NFE exome AF: 0.856

Gnomad OTH exome AF: 0.816

GnomAD4 exome AF: 0.810 AC: 483689 AN: 597038 Hom.: 210039 Cov.: 12 AF XY: 0.810 AC XY: 258092 AN XY: 318752

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.870

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.700

Gnomad4 SAS exome AF: 0.765

Gnomad4 FIN exome AF: 0.798

Gnomad4 NFE exome AF: 0.826

Gnomad4 OTH exome AF: 0.804

GnomAD4 genome AF: 0.823 AC: 115871 AN: 140808 Hom.: 48100 Cov.: 0 AF XY: 0.824 AC XY: 55728 AN XY: 67642

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.819

Alfa AF: 0.577 Hom.: 1706

Asia WGS AF: 0.694 AC: 1878 AN: 2708

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs11399505; hg19: chr5-96101066;