5-96786506-C-T

Position:

chr5-96786506-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000443439.7(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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D575G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.16 ( 2292 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31288 hom. )

Consequence

ERAP1
ENST00000443439.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.527

Variant links:

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]

ERAP1 links:

LOC124901031 (HGNC:):

LOC124901031 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	NM_001040458.3 linkuse as main transcript	c.1723G>A	p.Asp575Asn	missense_variant	12/19	ENST00000443439.7	NP_001035548.1
LOC124901031	XR_007058877.1 linkuse as main transcript	n.2111C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7 linkuse as main transcript	c.1723G>A	p.Asp575Asn	missense_variant	12/19	1	NM_001040458.3	ENSP00000406304	P1	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.1723G>A	p.Asp575Asn	missense_variant	12/20	1		ENSP00000296754		Q9NZ08-2
ERAP1	ENST00000507859.1 linkuse as main transcript	n.386G>A		non_coding_transcript_exon_variant	4/5	2
ERAP1	ENST00000514604.5 linkuse as main transcript	n.147G>A		non_coding_transcript_exon_variant	2/6	5

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24688

AN:

151994

Hom.:

2290

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.154

AC:

38756

AN:

251042

Hom.:

3589

AF XY:

0.156

AC XY:

21170

AN XY:

135682

show subpopulations

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 SAS exome

AF:

0.0963

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.:

AF XY:

0.196

AC XY:

141980

AN XY:

725024

show subpopulations

Gnomad4 AFR exome

AF:

0.0900

Gnomad4 AMR exome

AF:

0.0938

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.0451

Gnomad4 SAS exome

AF:

0.0972

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.162

AC:

24704

AN:

152110

Hom.:

2292

Cov.:

AF XY:

0.160

AC XY:

11879

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0951

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.0473

Gnomad4 SAS

AF:

0.0912

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.194

Hom.:

7592

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.57

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

1.0

N;N

REVEL

Benign

0.097

Sift

Benign

1.0

T;T

Sift4G

Benign

0.65

T;T

Polyphen

0.0

B;B

Vest4

0.037

MPC

0.072

ClinPred

0.0077

GERP RS

5.3

Varity_R

0.14

gMVP

0.34

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over