rs27044

Variant names:

• chr5-96783148-G-C
• rs27044
• NM_001040458.3:c.2188C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-96783148-G-C
• chr5-96783148-G-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001040458.3(ERAP1):​c.2188C>G​(p.Gln730Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,613,816 control chromosomes in the GnomAD database, including 413,964 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (37878 hom., cov: 32)
  • Exomes 𝑓: 0.72 (376086 hom.)
• Consequence: ERAP1 NM_001040458.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.778
• Publications: 192 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.956569E-5).
• BP6: Variant 5-96783148-G-C is Benign according to our data. Variant chr5-96783148-G-C is described in ClinVar as Benign. ClinVar VariationId is 2688532.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	NM_001040458.3	MANE Select	c.2188C>G	p.Gln730Glu	missense	Exon 15 of 19	NP_001035548.1	Q9NZ08-1
	ERAP1	NM_001349244.2		c.2188C>G	p.Gln730Glu	missense	Exon 15 of 20	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.2188C>G	p.Gln730Glu	missense	Exon 15 of 20	NP_057526.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.2188C>G	p.Gln730Glu	missense	Exon 15 of 19	ENSP00000406304.2	Q9NZ08-1
	ERAP1	ENST00000296754.7	TSL:1	c.2188C>G	p.Gln730Glu	missense	Exon 15 of 20	ENSP00000296754.3	Q9NZ08-2
	ERAP1	ENST00000853356.1		c.2188C>G	p.Gln730Glu	missense	Exon 15 of 19	ENSP00000523415.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106882 AN: 151950 Hom.: 37831 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.668

GnomAD2 exomes AF: 0.692 AC: 173885 AN: 251392 AF XY: 0.696

Gnomad AFR exome AF: 0.717

Gnomad AMR exome AF: 0.659

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.496

Gnomad FIN exome AF: 0.694

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.702

GnomAD4 exome AF: 0.716 AC: 1046529 AN: 1461746 Hom.: 376086 Cov.: 53 AF XY: 0.717 AC XY: 521283 AN XY: 727176

African (AFR) AF: 0.711 AC: 23796 AN: 33480

American (AMR) AF: 0.658 AC: 29434 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 18226 AN: 26134

East Asian (EAS) AF: 0.560 AC: 22232 AN: 39680

South Asian (SAS) AF: 0.719 AC: 62042 AN: 86256

European-Finnish (FIN) AF: 0.695 AC: 37105 AN: 53412

Middle Eastern (MID) AF: 0.728 AC: 4199 AN: 5768

European-Non Finnish (NFE) AF: 0.726 AC: 806991 AN: 1111904

Other (OTH) AF: 0.704 AC: 42504 AN: 60392

GnomAD4 genome AF: 0.704 AC: 106982 AN: 152070 Hom.: 37878 Cov.: 32 AF XY: 0.701 AC XY: 52097 AN XY: 74336

African (AFR) AF: 0.711 AC: 29505 AN: 41474

American (AMR) AF: 0.663 AC: 10133 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2428 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2801 AN: 5160

South Asian (SAS) AF: 0.722 AC: 3484 AN: 4826

European-Finnish (FIN) AF: 0.686 AC: 7237 AN: 10556

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49152 AN: 67980

Other (OTH) AF: 0.670 AC: 1412 AN: 2108

Alfa AF: 0.713 Hom.: 29211

Bravo AF: 0.698

TwinsUK AF: 0.731 AC: 2712

ALSPAC AF: 0.722 AC: 2783

ESP6500AA AF: 0.706 AC: 3111

ESP6500EA AF: 0.709 AC: 6094

ExAC AF: 0.694 AC: 84212

Asia WGS AF: 0.679 AC: 2360 AN: 3478

EpiCase AF: 0.730

EpiControl AF: 0.719

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.3
DANN	Benign	0.61
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.017	T
MetaRNN	Benign	0.000020	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.78
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.069
Sift	Benign	0.62	T
Sift4G	Benign	1.0	T
Polyphen		0.038	B
Vest4		0.039
MPC		0.080
ClinPred		0.00030	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.50
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: rs27044; hg19: chr5-96118852; COSMIC: COSV57085400; COSMIC: COSV57085400;