5-96826239-T-G

Variant names:

• chr5-96826239-T-G
• rs152280
• ENST00000501338.6:n.1782-3122A>C

Variant summary

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

The ENST00000501338.6(ENSG00000247121):​n.1782-3122A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,146 control chromosomes in the GnomAD database, including 40,660 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 0.73 (40660 hom., cov: 33)
• Consequence: ENSG00000247121 ENST00000501338.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	XM_011543484.3	c.-450-3119A>C		intron_variant	Intron 3 of 23		XP_011541786.1
ERAP1	XM_011543485.3	c.-270-11929A>C		intron_variant	Intron 3 of 22		XP_011541787.1
ERAP1	XM_017009581.2	c.-454-3119A>C		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.1782-3122A>C		intron_variant	Intron 2 of 3	2
ENSG00000247121	ENST00000502262.4	n.253-3122A>C		intron_variant	Intron 2 of 3	5
ENSG00000247121	ENST00000504056.5	n.192-11929A>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110310 AN: 152028 Hom.: 40619 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.726 AC: 110413 AN: 152146 Hom.: 40660 Cov.: 33 AF XY: 0.723 AC XY: 53763 AN XY: 74372

African (AFR) AF: 0.645 AC: 26751 AN: 41492

American (AMR) AF: 0.707 AC: 10803 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2348 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2537 AN: 5176

South Asian (SAS) AF: 0.689 AC: 3324 AN: 4822

European-Finnish (FIN) AF: 0.779 AC: 8237 AN: 10568

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.796 AC: 54144 AN: 68022

Other (OTH) AF: 0.710 AC: 1500 AN: 2112

Alfa AF: 0.765 Hom.: 19613

Bravo AF: 0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.012
DANN	Benign	0.48
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs152280; hg19: chr5-96161942;