Variant chr5-96774507-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001040458.3(ERAP1):c.*1889T>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 0.287 in 984,688 control chromosomes in the GnomAD database, including 42,210 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 0.23 ( 4353 hom., cov: 32)

Exomes 𝑓: 0.30 ( 37857 hom. )

Consequence

ERAP1
NM_001040458.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	NM_001040458.3 link	c.*1889T>A		3_prime_UTR_variant	19/19	ENST00000443439.7	NP_001035548.1	Q9NZ08-1
CAST	NM_001750.7 link	c.*1891A>T		3_prime_UTR_variant	32/32	ENST00000675179.1	NP_001741.4	P20810-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439 link	c.*1889T>A		3_prime_UTR_variant	19/19	1	NM_001040458.3	ENSP00000406304.2		Q9NZ08-1
CAST	ENST00000675179.1 link	c.*1891A>T		3_prime_UTR_variant	32/32		NM_001750.7	ENSP00000501872.1		P20810-6

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34238

AN:

152012

Hom.:

4350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.0478

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.298

AC:

248338

AN:

832558

Hom.:

37857

Cov.:

AF XY:

0.299

AC XY:

115056

AN XY:

384594

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.269

Gnomad4 EAS exome

AF:

0.0521

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.225

AC:

34249

AN:

152130

Hom.:

4353

Cov.:

AF XY:

0.220

AC XY:

16381

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.0482

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.117

Hom.:

212

Bravo

AF:

0.215

Asia WGS

AF:

0.133

AC:

460

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.75

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