rs149173

Variant names:

• chr5-96778789-T-C
• rs149173
• NM_001040458.3:c.2670+1634A>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.2670+1634A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,054 control chromosomes in the GnomAD database, including 4,379 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 (4379 hom., cov: 32)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 15 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]

CAST (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.341 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.2670+1634A>G		intron	N/A	NP_001035548.1	Q9NZ08-1
	ERAP1	NM_001349244.2		c.2670+1634A>G		intron	N/A	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.2670+1634A>G		intron	N/A	NP_057526.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.2670+1634A>G		intron	N/A	ENSP00000406304.2	Q9NZ08-1
	ERAP1	ENST00000296754.7	TSL:1	c.2670+1634A>G		intron	N/A	ENSP00000296754.3	Q9NZ08-2
	CAST	ENST00000510098.1	TSL:1	n.*438-533T>C		intron	N/A	ENSP00000427195.1	A0A0C4DGD1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33210 AN: 151936 Hom.: 4374 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.218 AC: 33216 AN: 152054 Hom.: 4379 Cov.: 32 AF XY: 0.224 AC XY: 16673 AN XY: 74322

African (AFR) AF: 0.0785 AC: 3258 AN: 41484

American (AMR) AF: 0.348 AC: 5320 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5164

South Asian (SAS) AF: 0.306 AC: 1471 AN: 4814

European-Finnish (FIN) AF: 0.280 AC: 2963 AN: 10572

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17255 AN: 67968

Other (OTH) AF: 0.234 AC: 493 AN: 2110

Alfa AF: 0.222 Hom.: 1725

Bravo AF: 0.219

Asia WGS AF: 0.241 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.068
DANN	Benign	0.60
PhyloP100		-1.9
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs149173;

hg19: chr5-96114493;

COSMIC: COSV57086329;

COSMIC: COSV57086329;