rs17481856

Variant names:

• chr5-96781104-G-A
• rs17481856
• NM_001040458.3:c.2542C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-96781104-G-A
• chr5-96781104-G-C
• chr5-96781104-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001040458.3(ERAP1):​c.2542C>T​(p.Leu848Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,464 control chromosomes in the GnomAD database, including 11,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (838 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10611 hom.)
• Consequence: ERAP1 NM_001040458.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.355
• Publications: 25 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-96781104-G-A is Benign according to our data. Variant chr5-96781104-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.355 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 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.2542C>T	p.Leu848Leu	synonymous	Exon 17 of 19	NP_001035548.1	Q9NZ08-1
	ERAP1	NM_001349244.2		c.2542C>T	p.Leu848Leu	synonymous	Exon 17 of 20	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.2542C>T	p.Leu848Leu	synonymous	Exon 17 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.2542C>T	p.Leu848Leu	synonymous	Exon 17 of 19	ENSP00000406304.2	Q9NZ08-1
	ERAP1	ENST00000296754.7	TSL:1	c.2542C>T	p.Leu848Leu	synonymous	Exon 17 of 20	ENSP00000296754.3	Q9NZ08-2
	ERAP1	ENST00000853356.1		c.2542C>T	p.Leu848Leu	synonymous	Exon 17 of 19	ENSP00000523415.1

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13879 AN: 151728 Hom.: 839 Cov.: 31

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.118

GnomAD2 exomes AF: 0.0998 AC: 25075 AN: 251366 AF XY: 0.103

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.0725

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.00103

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.116 AC: 169749 AN: 1461618 Hom.: 10611 Cov.: 33 AF XY: 0.116 AC XY: 84518 AN XY: 727114

African (AFR) AF: 0.0198 AC: 663 AN: 33480

American (AMR) AF: 0.0768 AC: 3433 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3311 AN: 26128

East Asian (EAS) AF: 0.000555 AC: 22 AN: 39666

South Asian (SAS) AF: 0.0807 AC: 6957 AN: 86250

European-Finnish (FIN) AF: 0.119 AC: 6333 AN: 53418

Middle Eastern (MID) AF: 0.113 AC: 653 AN: 5768

European-Non Finnish (NFE) AF: 0.127 AC: 141620 AN: 1111806

Other (OTH) AF: 0.112 AC: 6757 AN: 60382

GnomAD4 genome AF: 0.0914 AC: 13875 AN: 151846 Hom.: 838 Cov.: 31 AF XY: 0.0916 AC XY: 6794 AN XY: 74202

African (AFR) AF: 0.0221 AC: 914 AN: 41418

American (AMR) AF: 0.100 AC: 1527 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0847 AC: 406 AN: 4792

European-Finnish (FIN) AF: 0.126 AC: 1328 AN: 10506

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8811 AN: 67958

Other (OTH) AF: 0.117 AC: 244 AN: 2090

Alfa AF: 0.108 Hom.: 820

Bravo AF: 0.0872

Asia WGS AF: 0.0330 AC: 118 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.135

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.71
DANN	Benign	0.52
PhyloP100		0.35
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17481856; hg19: chr5-96116808;