5-96765327-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Position:

• chr5-96765327-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001750.7(CAST):​c.2037+28delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (892 hom., cov: 0)
  • Exomes 𝑓: 0.063 (101 hom.)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47

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]

CAST (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAST	NM_001750.7	c.2037+28delA		intron_variant		ENST00000675179.1	NP_001741.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000675179.1	c.2037+28delA		intron_variant			NM_001750.7	ENSP00000501872.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 12440 AN: 98640 Hom.: 892 Cov.: 0

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00643

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.00871 AC: 106 AN: 12164 Hom.: 1 AF XY: 0.00770 AC XY: 49 AN XY: 6366

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.00971

Gnomad EAS exome AF: 0.0424

Gnomad SAS exome AF: 0.0227

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00525

Gnomad OTH exome AF: 0.0158

GnomAD4 exome AF: 0.0631 AC: 25370 AN: 401916 Hom.: 101 Cov.: 0 AF XY: 0.0633 AC XY: 13661 AN XY: 215946

Gnomad4 AFR exome AF: 0.0531

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.0688

Gnomad4 EAS exome AF: 0.0546

Gnomad4 SAS exome AF: 0.0496

Gnomad4 FIN exome AF: 0.0602

Gnomad4 NFE exome AF: 0.0661

Gnomad4 OTH exome AF: 0.0705

GnomAD4 genome AF: 0.126 AC: 12437 AN: 98632 Hom.: 892 Cov.: 0 AF XY: 0.122 AC XY: 5509 AN XY: 45130

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00646

Gnomad4 SAS AF: 0.0904

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs59338324; hg19: chr5-96101031;