5-96786506-C-T

Variant names:

• chr5-96786506-C-T
• rs10050860
• NM_001040458.3:c.1723G>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.1723G>A​(p.Asp575Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,608,984 control chromosomes in the GnomAD database, including 33,580 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 0.16 (2292 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31288 hom.)
• Consequence: ERAP1 NM_001040458.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527
• Publications: 131 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]

LOC124901031 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011562407).
• BP6: Variant 5-96786506-C-T is Benign according to our data. Variant chr5-96786506-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688495.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 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.1723G>A	p.Asp575Asn	missense	Exon 12 of 19	NP_001035548.1	Q9NZ08-1
	ERAP1	NM_001349244.2		c.1723G>A	p.Asp575Asn	missense	Exon 12 of 20	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.1723G>A	p.Asp575Asn	missense	Exon 12 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.1723G>A	p.Asp575Asn	missense	Exon 12 of 19	ENSP00000406304.2	Q9NZ08-1
	ERAP1	ENST00000296754.7	TSL:1	c.1723G>A	p.Asp575Asn	missense	Exon 12 of 20	ENSP00000296754.3	Q9NZ08-2
	ERAP1	ENST00000853356.1		c.1723G>A	p.Asp575Asn	missense	Exon 12 of 19	ENSP00000523415.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24688 AN: 151994 Hom.: 2290 Cov.: 33

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.154 AC: 38756 AN: 251042 AF XY: 0.156

Gnomad AFR exome AF: 0.0936

Gnomad AMR exome AF: 0.0899

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.0495

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.198 AC: 289035 AN: 1456874 Hom.: 31288 Cov.: 31 AF XY: 0.196 AC XY: 141980 AN XY: 725024

African (AFR) AF: 0.0900 AC: 3009 AN: 33430

American (AMR) AF: 0.0938 AC: 4192 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3326 AN: 26108

East Asian (EAS) AF: 0.0451 AC: 1789 AN: 39666

South Asian (SAS) AF: 0.0972 AC: 8377 AN: 86172

European-Finnish (FIN) AF: 0.193 AC: 10284 AN: 53386

Middle Eastern (MID) AF: 0.0967 AC: 524 AN: 5420

European-Non Finnish (NFE) AF: 0.223 AC: 246738 AN: 1107760

Other (OTH) AF: 0.179 AC: 10796 AN: 60222

GnomAD4 genome AF: 0.162 AC: 24704 AN: 152110 Hom.: 2292 Cov.: 33 AF XY: 0.160 AC XY: 11879 AN XY: 74362

African (AFR) AF: 0.0951 AC: 3947 AN: 41488

American (AMR) AF: 0.140 AC: 2134 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3470

East Asian (EAS) AF: 0.0473 AC: 245 AN: 5182

South Asian (SAS) AF: 0.0912 AC: 440 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2157 AN: 10582

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14918 AN: 67974

Other (OTH) AF: 0.137 AC: 289 AN: 2106

Alfa AF: 0.187 Hom.: 10296

Bravo AF: 0.155

TwinsUK AF: 0.226 AC: 839

ALSPAC AF: 0.228 AC: 877

ESP6500AA AF: 0.103 AC: 452

ESP6500EA AF: 0.213 AC: 1831

ExAC AF: 0.155 AC: 18792

Asia WGS AF: 0.0930 AC: 323 AN: 3478

EpiCase AF: 0.204

EpiControl AF: 0.205

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	0.066
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.57	N
PhyloP100		0.53
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.097
Sift	Benign	1.0	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.037
MPC		0.072
ClinPred		0.0077	T
GERP RS		5.3
Varity_R		0.14
gMVP		0.34
Mutation Taster		=98/2	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: rs10050860; hg19: chr5-96122210; COSMIC: COSV57089586; COSMIC: COSV57089586;