rs151823

Variant names:

• chr5-96824289-A-C
• rs151823
• ENST00000501338.6:n.1782-1172T>G

Variant summary

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

The ENST00000501338.6(ENSG00000247121):​n.1782-1172T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,200 control chromosomes in the GnomAD database, including 61,794 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 0.90 (61794 hom., cov: 30)
• Consequence: ENSG00000247121 ENST00000501338.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 31 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	XM_011543484.3	c.-450-1169T>G		intron_variant	Intron 3 of 23		XP_011541786.1
ERAP1	XM_011543485.3	c.-270-9979T>G		intron_variant	Intron 3 of 22		XP_011541787.1
ERAP1	XM_017009581.2	c.-454-1169T>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.1782-1172T>G		intron_variant	Intron 2 of 3	2
ENSG00000247121	ENST00000502262.4	n.253-1172T>G		intron_variant	Intron 2 of 3	5
ENSG00000247121	ENST00000504056.5	n.192-9979T>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136440 AN: 152082 Hom.: 61734 Cov.: 30

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.897 AC: 136562 AN: 152200 Hom.: 61794 Cov.: 30 AF XY: 0.893 AC XY: 66465 AN XY: 74414

African (AFR) AF: 0.928 AC: 38545 AN: 41534

American (AMR) AF: 0.830 AC: 12695 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3110 AN: 3470

East Asian (EAS) AF: 0.551 AC: 2845 AN: 5168

South Asian (SAS) AF: 0.845 AC: 4071 AN: 4818

European-Finnish (FIN) AF: 0.893 AC: 9458 AN: 10594

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62859 AN: 68018

Other (OTH) AF: 0.891 AC: 1873 AN: 2102

Alfa AF: 0.912 Hom.: 140391

Bravo AF: 0.891

Asia WGS AF: 0.746 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		-0.65

Splicing

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

Other links and lift over

dbSNP: rs151823; hg19: chr5-96159992;