chr5-96765327-T-TA

Position:

• chr5-96765327-T-TA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001750.7(CAST):​c.2037+28dupA 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 0.0037 (6 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00368 AC: 364 AN: 98898 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00321

Gnomad SAS AF: 0.00623

Gnomad FIN AF: 0.000371

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00105

Gnomad OTH AF: 0.00230

GnomAD4 exome AF: 0.00121 AC: 501 AN: 413038 Hom.: 0 Cov.: 0 AF XY: 0.00124 AC XY: 276 AN XY: 222390

Gnomad4 AFR exome AF: 0.00334

Gnomad4 AMR exome AF: 0.000658

Gnomad4 ASJ exome AF: 0.00163

Gnomad4 EAS exome AF: 0.00246

Gnomad4 SAS exome AF: 0.00305

Gnomad4 FIN exome AF: 0.000852

Gnomad4 NFE exome AF: 0.000857

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00369 AC: 365 AN: 98890 Hom.: 6 Cov.: 0 AF XY: 0.00371 AC XY: 168 AN XY: 45256

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.00187

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00323

Gnomad4 SAS AF: 0.00661

Gnomad4 FIN AF: 0.000371

Gnomad4 NFE AF: 0.00105

Gnomad4 OTH AF: 0.00229

ClinVar

Not reported in ClinVar

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: rs59338324; hg19: chr5-96101031;