5-96863790-A-G

Variant names:

• chr5-96863790-A-G
• rs2927612
• ENST00000501338.6:n.1781+9496T>C

Variant summary

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

The ENST00000501338.6(ENSG00000247121):​n.1781+9496T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,080 control chromosomes in the GnomAD database, including 740 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 0.090 (740 hom., cov: 32)
• Consequence: ENSG00000247121 ENST00000501338.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	XM_011543484.3	c.-451+9496T>C		intron_variant	Intron 3 of 23		XP_011541786.1
ERAP1	XM_011543485.3	c.-271+9496T>C		intron_variant	Intron 3 of 22		XP_011541787.1
ERAP1	XM_017009581.2	c.-455+9496T>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.1781+9496T>C		intron_variant	Intron 2 of 3	2
ENSG00000247121	ENST00000502262.4	n.252+9496T>C		intron_variant	Intron 2 of 3	5
ENSG00000247121	ENST00000504056.5	n.191+9496T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13636 AN: 151962 Hom.: 739 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0814

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0897 AC: 13642 AN: 152080 Hom.: 740 Cov.: 32 AF XY: 0.0920 AC XY: 6839 AN XY: 74354

African (AFR) AF: 0.0373 AC: 1548 AN: 41518

American (AMR) AF: 0.0730 AC: 1113 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0814 AC: 282 AN: 3464

East Asian (EAS) AF: 0.0338 AC: 175 AN: 5176

South Asian (SAS) AF: 0.104 AC: 501 AN: 4816

European-Finnish (FIN) AF: 0.166 AC: 1753 AN: 10574

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8004 AN: 67974

Other (OTH) AF: 0.0707 AC: 149 AN: 2108

Alfa AF: 0.101 Hom.: 2718

Bravo AF: 0.0795

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs2927612; hg19: chr5-96199493;