rs27038

Positions:

• chr5-96777250-A-G

Variant summary

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

The NM_001040458.3(ERAP1):​c.2671-699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,196 control chromosomes in the GnomAD database, including 51,103 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 0.82 (51103 hom., cov: 32)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.2671-699T>C		intron_variant		ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.2671-699T>C		intron_variant		1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.2671-699T>C		intron_variant		1		ENSP00000296754.3
CAST	ENST00000510098.1	n.*437+296A>G		intron_variant		1		ENSP00000427195.1
ERAP1	ENST00000512852.1	c.205-699T>C		intron_variant		3		ENSP00000425381.1

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124216 AN: 152076 Hom.: 51052 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.814

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.817 AC: 124318 AN: 152196 Hom.: 51103 Cov.: 32 AF XY: 0.817 AC XY: 60787 AN XY: 74402

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.815

Alfa AF: 0.847 Hom.: 43411

Bravo AF: 0.818

Asia WGS AF: 0.749 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.62

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: rs27038; hg19: chr5-96112954;