5-96808142-C-T

Position:

• chr5-96808142-C-T

Variant summary

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

The XR_007058879.1(LOC124901033):​n.685C>T 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 0.149 in 473,010 control chromosomes in the GnomAD database, including 17,055 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 0.38 (9520 hom., cov: 28)
  • Exomes 𝑓: 0.054 (7535 hom.)
• Consequence: LOC124901033 XR_007058879.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901033	XR_007058879.1	n.685C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000296754.7			upstream_gene_variant		1		ENSP00000296754

Frequencies

GnomAD3 genomes AF: 0.376 AC: 52310 AN: 139124 Hom.: 9511 Cov.: 28

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.0539 AC: 17983 AN: 333800 Hom.: 7535 Cov.: 0 AF XY: 0.0564 AC XY: 8705 AN XY: 154434

Gnomad4 AFR exome AF: 0.0293

Gnomad4 AMR exome AF: 0.0183

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.0296

Gnomad4 SAS exome AF: 0.0611

Gnomad4 FIN exome AF: 0.0152

Gnomad4 NFE exome AF: 0.0546

Gnomad4 OTH exome AF: 0.0504

GnomAD4 genome AF: 0.376 AC: 52341 AN: 139210 Hom.: 9520 Cov.: 28 AF XY: 0.374 AC XY: 25108 AN XY: 67092

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.379

Alfa AF: 0.312 Hom.: 1465

Bravo AF: 0.340

Asia WGS AF: 0.254 AC: 778 AN: 3058

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.54
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs151949; hg19: chr5-96143845;