rs13167972

chr5-96761124-A-G

Variant summary

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

The ENST00000296754.7(ERAP1):c.*2076T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,022 control chromosomes in the GnomAD database, including 9,224 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 0.34 (9215 hom., cov: 32)
  • Exomes 𝑓: 0.35 (9 hom.)
• Consequence: ERAP1 ENST00000296754.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.78

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.1834-1150A>G		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.1834-1150A>G		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52130 AN: 151766 Hom.: 9208 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.353 AC: 48 AN: 136 Hom.: 9 Cov.: 0 AF XY: 0.392 AC XY: 29 AN XY: 74

Gnomad4 EAS exome AF: 0.353

GnomAD4 genome AF: 0.343 AC: 52162 AN: 151886 Hom.: 9215 Cov.: 32 AF XY: 0.340 AC XY: 25201 AN XY: 74200

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.334

Alfa AF: 0.370 Hom.: 2246

Bravo AF: 0.336

Asia WGS AF: 0.249 AC: 855 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.11
Dann	Benign	0.36

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: rs13167972; hg19: chr5-96096828;