rs3822682

Positions:

• chr5-96763054-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000296754.7(ERAP1):​c.*146G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 757,636 control chromosomes in the GnomAD database, including 3,133 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.093 (793 hom., cov: 32)
  • Exomes 𝑓: 0.080 (2340 hom.)
• Consequence: ERAP1 ENST00000296754.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

Genes affected

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: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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.1932+682C>T		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.1932+682C>T		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14191 AN: 152096 Hom.: 794 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.0798 AC: 48340 AN: 605422 Hom.: 2340 Cov.: 0 AF XY: 0.0834 AC XY: 27563 AN XY: 330650

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0438

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0430

Gnomad4 NFE exome AF: 0.0727

Gnomad4 OTH exome AF: 0.0873

GnomAD4 genome AF: 0.0933 AC: 14202 AN: 152214 Hom.: 793 Cov.: 32 AF XY: 0.0933 AC XY: 6944 AN XY: 74428

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0700

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0815 Hom.: 159

Bravo AF: 0.0964

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3822682; hg19: chr5-96098758;