rs469783

Variant names:

• chr5-96785820-C-T
• rs469783
• NM_001040458.3:c.1911G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-96785820-C-T
• chr5-96785820-C-A
• chr5-96785820-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001040458.3(ERAP1):​c.1911G>A​(p.Ala637Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,613,624 control chromosomes in the GnomAD database, including 259,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24113 hom., cov: 31)
  • Exomes 𝑓: 0.57 (235606 hom.)
• Consequence: ERAP1 NM_001040458.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.381
• Publications: 59 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]

ENSG00000248734 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 5-96785820-C-T is Benign according to our data. Variant chr5-96785820-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.381 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 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.1911G>A	p.Ala637Ala	synonymous	Exon 13 of 19	NP_001035548.1	Q9NZ08-1
	ERAP1	NM_001349244.2		c.1911G>A	p.Ala637Ala	synonymous	Exon 13 of 20	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.1911G>A	p.Ala637Ala	synonymous	Exon 13 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.1911G>A	p.Ala637Ala	synonymous	Exon 13 of 19	ENSP00000406304.2	Q9NZ08-1
	ERAP1	ENST00000296754.7	TSL:1	c.1911G>A	p.Ala637Ala	synonymous	Exon 13 of 20	ENSP00000296754.3	Q9NZ08-2
	ERAP1	ENST00000853356.1		c.1911G>A	p.Ala637Ala	synonymous	Exon 13 of 19	ENSP00000523415.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85363 AN: 151846 Hom.: 24076 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.498

GnomAD2 exomes AF: 0.554 AC: 139079 AN: 251214 AF XY: 0.551

Gnomad AFR exome AF: 0.587

Gnomad AMR exome AF: 0.577

Gnomad ASJ exome AF: 0.442

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.579

Gnomad NFE exome AF: 0.564

Gnomad OTH exome AF: 0.540

GnomAD4 exome AF: 0.566 AC: 827802 AN: 1461660 Hom.: 235606 Cov.: 53 AF XY: 0.565 AC XY: 410624 AN XY: 727118

African (AFR) AF: 0.574 AC: 19228 AN: 33478

American (AMR) AF: 0.574 AC: 25661 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 11637 AN: 26134

East Asian (EAS) AF: 0.514 AC: 20407 AN: 39690

South Asian (SAS) AF: 0.527 AC: 45491 AN: 86252

European-Finnish (FIN) AF: 0.579 AC: 30893 AN: 53398

Middle Eastern (MID) AF: 0.421 AC: 2430 AN: 5768

European-Non Finnish (NFE) AF: 0.575 AC: 638938 AN: 1111840

Other (OTH) AF: 0.548 AC: 33117 AN: 60386

GnomAD4 genome AF: 0.562 AC: 85449 AN: 151964 Hom.: 24113 Cov.: 31 AF XY: 0.562 AC XY: 41721 AN XY: 74282

African (AFR) AF: 0.579 AC: 23987 AN: 41440

American (AMR) AF: 0.550 AC: 8397 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1561 AN: 3466

East Asian (EAS) AF: 0.512 AC: 2649 AN: 5170

South Asian (SAS) AF: 0.536 AC: 2580 AN: 4814

European-Finnish (FIN) AF: 0.573 AC: 6046 AN: 10552

Middle Eastern (MID) AF: 0.386 AC: 112 AN: 290

European-Non Finnish (NFE) AF: 0.570 AC: 38732 AN: 67940

Other (OTH) AF: 0.500 AC: 1059 AN: 2116

Alfa AF: 0.552 Hom.: 23131

Bravo AF: 0.558

Asia WGS AF: 0.565 AC: 1967 AN: 3478

EpiCase AF: 0.558

EpiControl AF: 0.544

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	-0.41
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		-0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs469783; hg19: chr5-96121524; COSMIC: COSV57085666; COSMIC: COSV57085666;