5-96765327-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

Position:

• chr5-96765327-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001750.7(CAST):​c.2037+26_2037+28dupAAA 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 0.000010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000022 (0 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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAST	NM_001750.7	c.2037+26_2037+28dupAAA		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+26_2037+28dupAAA		intron_variant			NM_001750.7	ENSP00000501872.1

Frequencies

GnomAD3 genomes AF: 0.0000101 AC: 1 AN: 98902 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000198

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000218 AC: 9 AN: 413376 Hom.: 0 Cov.: 0 AF XY: 0.0000180 AC XY: 4 AN XY: 222578

Gnomad4 AFR exome AF: 0.000108

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000431

Gnomad4 SAS exome AF: 0.0000972

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000111

Gnomad4 OTH exome AF: 0.0000455

GnomAD4 genome AF: 0.0000101 AC: 1 AN: 98902 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 45250

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000198

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;