XR_007058879.1:n.685C>A

Variant names:

• chr5-96808142-C-A
• rs151949
• XR_007058879.1:n.685C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XR_007058879.1(LOC124901033):​n.685C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 473,060 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000014 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: LOC124901033 XR_007058879.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 10 publications found

Genes affected

LOC124901033 (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443439.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	NM_001198541.3		c.-17-4199G>T		intron	N/A	NP_001185470.1
	ERAP1	NM_001040458.3	MANE Select	c.-300G>T		upstream_gene	N/A	NP_001035548.1
	ERAP1	NM_001349244.2		c.-296G>T		upstream_gene	N/A	NP_001336173.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000294423	ENST00000723519.1		n.112+44C>A		intron	N/A
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.-300G>T		upstream_gene	N/A	ENSP00000406304.2
	ERAP1	ENST00000296754.7	TSL:1	c.-300G>T		upstream_gene	N/A	ENSP00000296754.3

Frequencies

GnomAD3 genomes AF: 0.0000144 AC: 2 AN: 139260 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000304

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000300 AC: 1 AN: 333800 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 154434

African (AFR) AF: 0.00 AC: 0 AN: 8248

American (AMR) AF: 0.00 AC: 0 AN: 602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1874

East Asian (EAS) AF: 0.00 AC: 0 AN: 1960

South Asian (SAS) AF: 0.00 AC: 0 AN: 6232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 570

European-Non Finnish (NFE) AF: 0.00000330 AC: 1 AN: 302940

Other (OTH) AF: 0.00 AC: 0 AN: 11242

GnomAD4 genome AF: 0.0000144 AC: 2 AN: 139260 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 67084

African (AFR) AF: 0.00 AC: 0 AN: 36470

American (AMR) AF: 0.00 AC: 0 AN: 13270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 4438

South Asian (SAS) AF: 0.00 AC: 0 AN: 4358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000304 AC: 2 AN: 65816

Other (OTH) AF: 0.00 AC: 0 AN: 1930

Alfa AF: 0.00 Hom.: 3062

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.42
DANN	Benign	0.52
PhyloP100		-1.8
PromoterAI		0.0069	Neutral

Splicing

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

Other links and lift over

dbSNP: rs151949; hg19: chr5-96143845;