NM_001750.7:c.2037+17_2037+28delAAAAAAAAAAAA

Variant names:

• chr5-96765327-TAAAAAAAAAAAA-T
• rs59338324
• NM_001750.7:c.2037+17_2037+28delAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001750.7(CAST):​c.2037+17_2037+28delAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000968 in 413,384 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001750.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAST	NM_001750.7	MANE Select	c.2037+17_2037+28delAAAAAAAAAAAA		intron	N/A	NP_001741.4
	ERAP1	NM_001349244.2		c.2819-2111_2819-2100delTTTTTTTTTTTT		intron	N/A	NP_001336173.1
	ERAP1	NM_016442.5		c.2819-2111_2819-2100delTTTTTTTTTTTT		intron	N/A	NP_057526.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAST	ENST00000675179.1	MANE Select	c.2037+3_2037+14delAAAAAAAAAAAA		splice_region intron	N/A	ENSP00000501872.1
	ERAP1	ENST00000296754.7	TSL:1	c.2819-2111_2819-2100delTTTTTTTTTTTT		intron	N/A	ENSP00000296754.3
	CAST	ENST00000341926.7	TSL:1	c.1788+3_1788+14delAAAAAAAAAAAA		splice_region intron	N/A	ENSP00000339914.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000968 AC: 4 AN: 413384 Hom.: 0 AF XY: 0.0000135 AC XY: 3 AN XY: 222580

African (AFR) AF: 0.00 AC: 0 AN: 9286

American (AMR) AF: 0.00 AC: 0 AN: 13674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11092

East Asian (EAS) AF: 0.00 AC: 0 AN: 23220

South Asian (SAS) AF: 0.0000324 AC: 1 AN: 30868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1706

European-Non Finnish (NFE) AF: 0.0000111 AC: 3 AN: 271032

Other (OTH) AF: 0.00 AC: 0 AN: 21970

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59338324; hg19: chr5-96101031;