rs1981846

Positions:

• chr5-96933158-C-A
• chr5-96933158-C-T

Variant summary

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

The XM_011543484.3(ERAP1):​c.-702+964G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 150,100 control chromosomes in the GnomAD database, including 18,728 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 0.50 (18728 hom., cov: 28)
• Consequence: ERAP1 XM_011543484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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]

ENSG00000247121 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	XM_011543484.3	c.-702+964G>T		intron_variant			XP_011541786.1
ERAP1	XM_011543485.3	c.-522+964G>T		intron_variant			XP_011541787.1
ERAP1	XM_017009581.2	c.-548+964G>T		intron_variant			XP_016865070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000247121	ENST00000501338.5	n.1688+964G>T		intron_variant		2
ENSG00000247121	ENST00000655392.1	n.818+964G>T		intron_variant
ENSG00000247121	ENST00000656950.1	n.834+964G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.497 AC: 74539 AN: 149996 Hom.: 18685 Cov.: 28

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.497 AC: 74643 AN: 150100 Hom.: 18728 Cov.: 28 AF XY: 0.494 AC XY: 36126 AN XY: 73122

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.488

Alfa AF: 0.479 Hom.: 8093

Bravo AF: 0.494

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.8
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1981846; hg19: chr5-96268862;