rs34750

Variant names:

• chr5-96807103-G-C
• rs34750
• NM_001040458.3:c.-18+757C>G

Variant summary

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

The NM_001040458.3(ERAP1):​c.-18+757C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,996 control chromosomes in the GnomAD database, including 30,948 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 0.63 (30948 hom., cov: 31)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 14 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.-18+757C>G		intron_variant	Intron 1 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.-18+757C>G		intron_variant	Intron 1 of 18	1	NM_001040458.3	ENSP00000406304.2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95695 AN: 151878 Hom.: 30934 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.630 AC: 95745 AN: 151996 Hom.: 30948 Cov.: 31 AF XY: 0.627 AC XY: 46604 AN XY: 74304

African (AFR) AF: 0.511 AC: 21159 AN: 41412

American (AMR) AF: 0.585 AC: 8946 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2520 AN: 5166

South Asian (SAS) AF: 0.548 AC: 2643 AN: 4822

European-Finnish (FIN) AF: 0.717 AC: 7581 AN: 10566

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48871 AN: 67956

Other (OTH) AF: 0.617 AC: 1304 AN: 2114

Alfa AF: 0.672 Hom.: 4315

Bravo AF: 0.615

Asia WGS AF: 0.569 AC: 1981 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	6.9
DANN	Benign	0.44
PhyloP100		1.6
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: rs34750; hg19: chr5-96142806;