dbSNP rs13167972: ERAP1:c.*2076T>C (chr5-96761124-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016442.5(ERAP1):c.*2076T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,022 control chromosomes in the GnomAD database, including 9,224 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 0.34 ( 9215 hom., cov: 32)

Exomes 𝑓: 0.35 ( 9 hom. )

Consequence

ERAP1
NM_016442.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.78

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAST	NM_001750.7 link	c.1834-1150A>G		intron_variant	Intron 24 of 31	ENST00000675179.1	NP_001741.4	P20810-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000675179.1 link	c.1834-1150A>G		intron_variant	Intron 24 of 31		NM_001750.7	ENSP00000501872.1		P20810-6

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52130

AN:

151766

Hom.:

9208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.353

AC:

AN:

136

Hom.:

Cov.:

AF XY:

0.392

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AF:

0.353

AC:

AN:

136

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AC:

AN:

Gnomad4 NFE exome

AC:

AN:

Gnomad4 Remaining exome

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.343

AC:

52162

AN:

151886

Hom.:

9215

Cov.:

AF XY:

0.340

AC XY:

25201

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.304

AC:

0.304222

AN:

0.304222

Gnomad4 AMR

AF:

0.288

AC:

0.288416

AN:

0.288416

Gnomad4 ASJ

AF:

0.407

AC:

0.406916

AN:

0.406916

Gnomad4 EAS

AF:

0.107

AC:

0.107019

AN:

0.107019

Gnomad4 SAS

AF:

0.350

AC:

0.35027

AN:

0.35027

Gnomad4 FIN

AF:

0.338

AC:

0.338004

AN:

0.338004

Gnomad4 NFE

AF:

0.394

AC:

0.393598

AN:

0.393598

Gnomad4 OTH

AF:

0.334

AC:

0.33428

AN:

0.33428

Heterozygous variant carriers

1732

3464

5197

6929

8661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.365

Hom.:

2555

Bravo

AF:

0.336

Asia WGS

AF:

0.249

AC:

855

AN:

3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.11

DANN

Benign

0.36

Mutation Taster

=100/0

polymorphism (auto)

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