chr5-96765327-TAAAAA-T

Position:

• chr5-96765327-TAAAAA-T

Variant summary

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

The NM_001750.7(CAST):​c.2037+24_2037+28delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 502,106 control chromosomes in the GnomAD database, including 178 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.072 (178 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: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAST	NM_001750.7	c.2037+24_2037+28delAAAAA		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+24_2037+28delAAAAA		intron_variant			NM_001750.7	ENSP00000501872.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 13 AN: 98896 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000110

Gnomad ASJ AF: 0.000366

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00260

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000594

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0313 AC: 381 AN: 12164 Hom.: 14 AF XY: 0.0331 AC XY: 211 AN XY: 6366

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.0306

Gnomad ASJ exome AF: 0.0170

Gnomad EAS exome AF: 0.0230

Gnomad SAS exome AF: 0.0103

Gnomad FIN exome AF: 0.00535

Gnomad NFE exome AF: 0.0518

Gnomad OTH exome AF: 0.0263

GnomAD4 exome AF: 0.0724 AC: 29192 AN: 403218 Hom.: 178 AF XY: 0.0732 AC XY: 15879 AN XY: 216804

Gnomad4 AFR exome AF: 0.0825

Gnomad4 AMR exome AF: 0.0998

Gnomad4 ASJ exome AF: 0.0747

Gnomad4 EAS exome AF: 0.0731

Gnomad4 SAS exome AF: 0.0790

Gnomad4 FIN exome AF: 0.0550

Gnomad4 NFE exome AF: 0.0715

Gnomad4 OTH exome AF: 0.0743

GnomAD4 genome AF: 0.000131 AC: 13 AN: 98888 Hom.: 0 Cov.: 0 AF XY: 0.000199 AC XY: 9 AN XY: 45258

Gnomad4 AFR AF: 0.0000394

Gnomad4 AMR AF: 0.000110

Gnomad4 ASJ AF: 0.000366

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00260

Gnomad4 NFE AF: 0.0000594

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;