rs26616

Variant names:

• chr5-96797889-C-G
• rs26616
• NM_001040458.3:c.664-580G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040458.3(ERAP1):​c.664-580G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,946 control chromosomes in the GnomAD database, including 3,832 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 0.22 (3832 hom., cov: 33)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.664-580G>C		intron_variant	Intron 3 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.664-580G>C		intron_variant	Intron 3 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.664-580G>C		intron_variant	Intron 3 of 19	1		ENSP00000296754.3
ERAP1	ENST00000503921.5	c.-60-580G>C		intron_variant	Intron 2 of 2	4		ENSP00000427025.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33844 AN: 151828 Hom.: 3831 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.223 AC: 33863 AN: 151946 Hom.: 3832 Cov.: 33 AF XY: 0.222 AC XY: 16474 AN XY: 74270

African (AFR) AF: 0.207 AC: 8584 AN: 41396

American (AMR) AF: 0.184 AC: 2808 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1397 AN: 5168

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4814

European-Finnish (FIN) AF: 0.216 AC: 2281 AN: 10548

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16267 AN: 67958

Other (OTH) AF: 0.227 AC: 480 AN: 2110

Alfa AF: 0.238 Hom.: 537

Bravo AF: 0.215

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.64
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs26616; hg19: chr5-96133592;