Variant rs10515248 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001040458.3(ERAP1):c.*95G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,544,294 control chromosomes in the GnomAD database, including 10,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.091 ( 827 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10084 hom. )

Consequence

ERAP1
NM_001040458.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0390

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:

CAST (HGNC:1515): (calpastatin) The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1-4), and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

CAST 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 (BayesDel_noAF=-0.65).

BP6

Variant 5-96776301-C-T is Benign according to our data. Variant chr5-96776301-C-T is described in ClinVar as [Benign]. Clinvar id is 2688516.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 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.*95G>A		3_prime_UTR_variant	19/19	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7 linkuse as main transcript	c.*95G>A	3_prime_UTR_variant	19/19	1	NM_001040458.3	ENSP00000406304	P1	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.2818+103G>A	intron_variant		1		ENSP00000296754		Q9NZ08-2
CAST	ENST00000510098.1 linkuse as main transcript	c.*351-567C>T	intron_variant, NMD_transcript_variant		1		ENSP00000427195
ERAP1	ENST00000512852.1 linkuse as main transcript	c.354+103G>A	intron_variant		3		ENSP00000425381

Frequencies

GnomAD3 genomes

AF:

0.0909

AC:

13823

AN:

152050

Hom.:

828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0829

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.116

AC:

161975

AN:

1392126

Hom.:

10084

Cov.:

AF XY:

0.116

AC XY:

79859

AN XY:

685950

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.0784

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.000796

Gnomad4 SAS exome

AF:

0.0799

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.0908

AC:

13819

AN:

152168

Hom.:

827

Cov.:

AF XY:

0.0910

AC XY:

6771

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0220

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0832

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.124

Hom.:

1625

Bravo

AF:

0.0865

Asia WGS

AF:

0.0370

AC:

131

AN:

3478

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 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.5

DANN

Benign

0.78

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