5-96808142-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.-300G>A		upstream_gene_variant		ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.-300G>A		upstream_gene_variant		1	NM_001040458.3	ENSP00000406304.2

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

African (AFR) AF: 0.0293 AC: 242 AN: 8248

American (AMR) AF: 0.0183 AC: 11 AN: 602

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 124 AN: 1874

East Asian (EAS) AF: 0.0296 AC: 58 AN: 1960

South Asian (SAS) AF: 0.0611 AC: 381 AN: 6232

European-Finnish (FIN) AF: 0.0152 AC: 2 AN: 132

Middle Eastern (MID) AF: 0.104 AC: 59 AN: 570

European-Non Finnish (NFE) AF: 0.0546 AC: 16539 AN: 302940

Other (OTH) AF: 0.0504 AC: 567 AN: 11242

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

African (AFR) AF: 0.338 AC: 12338 AN: 36538

American (AMR) AF: 0.317 AC: 4204 AN: 13280

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1449 AN: 3380

East Asian (EAS) AF: 0.317 AC: 1401 AN: 4420

South Asian (SAS) AF: 0.434 AC: 1884 AN: 4344

European-Finnish (FIN) AF: 0.399 AC: 3361 AN: 8414

Middle Eastern (MID) AF: 0.462 AC: 123 AN: 266

European-Non Finnish (NFE) AF: 0.404 AC: 26557 AN: 65752

Other (OTH) AF: 0.379 AC: 735 AN: 1940

Alfa AF: 0.345 Hom.: 3062

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
PhyloP100		-1.8
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism

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;