5-96796640-T-C

Position:

• chr5-96796640-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040458.3(ERAP1):​c.798+535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,954 control chromosomes in the GnomAD database, including 23,881 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 0.56 (23881 hom., cov: 31)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3	c.798+535A>G		intron_variant		ENST00000443439.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.798+535A>G		intron_variant		1	NM_001040458.3	P1
ERAP1	ENST00000296754.7	c.798+535A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84901 AN: 151836 Hom.: 23852 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.554

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 84964 AN: 151954 Hom.: 23881 Cov.: 31 AF XY: 0.558 AC XY: 41478 AN XY: 74274

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.553

Alfa AF: 0.569 Hom.: 23085

Bravo AF: 0.555

Asia WGS AF: 0.536 AC: 1866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.27

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

Other links and lift over

dbSNP: rs26499; hg19: chr5-96132343;