chr5-96824289-A-C

Position:

• chr5-96824289-A-C

Variant summary

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

The XM_011543484.3(ERAP1):​c.-450-1169T>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: ERAP1 XM_011543484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

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=-0.89).
• 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/exons	MANE	Protein	UniProt
ERAP1	XM_011543484.3	c.-450-1169T>G		intron_variant			XP_011541786.1
ERAP1	XM_011543485.3	c.-270-9979T>G		intron_variant			XP_011541787.1
ERAP1	XM_017009581.2	c.-454-1169T>G		intron_variant			XP_016865070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000247121	ENST00000501338.5	n.1782-1172T>G		intron_variant		2
ENSG00000247121	ENST00000502262.4	n.253-1172T>G		intron_variant		5
ENSG00000247121	ENST00000504056.5	n.192-9979T>G		intron_variant		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

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.891

Alfa AF: 0.915 Hom.: 40795

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs151823; hg19: chr5-96159992;