5-96765331-A-AAAAAAAAAAAAAAAAAAAAAAT

Variant names:

• chr5-96765331-A-AAAAAAAAAAAAAAAAAAAAAAT
• NM_001750.7:c.2037+27_2037+28insTAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000675179.1(CAST):​c.2037+6_2037+7insAAAAAAAAAAAAAAAAAAAAAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CAST ENST00000675179.1 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 5-96765331-A-AAAAAAAAAAAAAAAAAAAAAAT is Benign according to our data. Variant chr5-96765331-A-AAAAAAAAAAAAAAAAAAAAAAT is described in ClinVar as Likely_benign. ClinVar VariationId is 2749807.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000675179.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAST	NM_001750.7	MANE Select	c.2037+27_2037+28insTAAAAAAAAAAAAAAAAAAAAA		intron	N/A	NP_001741.4
	ERAP1	NM_001349244.2		c.2819-2104_2819-2103insATTTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.2819-2104_2819-2103insATTTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_057526.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAST	ENST00000675179.1	MANE Select	c.2037+6_2037+7insAAAAAAAAAAAAAAAAAAAAAT		splice_region intron	N/A	ENSP00000501872.1
	ERAP1	ENST00000296754.7	TSL:1	c.2819-2104_2819-2103insATTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000296754.3	Q9NZ08-2
	CAST	ENST00000341926.7	TSL:1	c.1788+6_1788+7insAAAAAAAAAAAAAAAAAAAAAT		splice_region intron	N/A	ENSP00000339914.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 10

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.061

Splicing

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

Other links and lift over

hg19: chr5-96101035;