Variant 5-96775667-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001040458.3(ERAP1):c.*729C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 241,920 control chromosomes in the GnomAD database, including 8,782 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 ( 4344 hom., cov: 33)

Exomes 𝑓: 0.30 ( 4438 hom. )

Consequence

ERAP1
NM_001040458.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.123

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3 linkuse as main transcript	c.*729C>T		3_prime_UTR_variant	19/19	ENST00000443439.7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7 linkuse as main transcript	c.*729C>T	3_prime_UTR_variant	19/19	1	NM_001040458.3	P1	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.2818+737C>T	intron_variant		1			Q9NZ08-2
CAST	ENST00000510098.1 linkuse as main transcript	c.*351-1201G>A	intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34189

AN:

152058

Hom.:

4341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0477

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.302

AC:

27135

AN:

89744

Hom.:

4438

Cov.:

AF XY:

0.301

AC XY:

13117

AN XY:

43522

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.0455

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.423

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.225

AC:

34200

AN:

152176

Hom.:

4344

Cov.:

AF XY:

0.220

AC XY:

16354

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.0480

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.303

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.275

Hom.:

3638

Bravo

AF:

0.214

Asia WGS

AF:

0.133

AC:

462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.6

DANN

Benign

0.80

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over