ENST00000501338.6:n.1782-7206A>G

Variant names:

• chr5-96830323-T-C
• rs41135
• ENST00000501338.6:n.1782-7206A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000501338.6(ENSG00000247121):​n.1782-7206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,018 control chromosomes in the GnomAD database, including 13,131 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 0.41 (13131 hom., cov: 32)
• Consequence: ENSG00000247121 ENST00000501338.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 29 publications found

Genes affected

ENSG00000247121 (HGNC:):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	XM_011543484.3	c.-450-7203A>G		intron_variant	Intron 3 of 23		XP_011541786.1
ERAP1	XM_011543485.3	c.-270-16013A>G		intron_variant	Intron 3 of 22		XP_011541787.1
ERAP1	XM_017009581.2	c.-454-7203A>G		intron_variant	Intron 2 of 22		XP_016865070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000247121	ENST00000501338.6	n.1782-7206A>G		intron_variant	Intron 2 of 3	2
ENSG00000247121	ENST00000502262.4	n.253-7206A>G		intron_variant	Intron 2 of 3	5
ENSG00000247121	ENST00000504056.5	n.192-16013A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62119 AN: 151902 Hom.: 13124 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.409 AC: 62160 AN: 152018 Hom.: 13131 Cov.: 32 AF XY: 0.408 AC XY: 30334 AN XY: 74310

African (AFR) AF: 0.317 AC: 13161 AN: 41462

American (AMR) AF: 0.394 AC: 6022 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1130 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1805 AN: 5170

South Asian (SAS) AF: 0.369 AC: 1780 AN: 4822

European-Finnish (FIN) AF: 0.467 AC: 4933 AN: 10556

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32119 AN: 67930

Other (OTH) AF: 0.389 AC: 819 AN: 2108

Alfa AF: 0.444 Hom.: 46476

Bravo AF: 0.395

Asia WGS AF: 0.406 AC: 1411 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	2.1
DANN	Benign	0.44
PhyloP100		-0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41135; hg19: chr5-96166026;