chr5-96785702-A-C

Variant names:

• chr5-96785702-A-C
• rs469876
• NM_001040458.3:c.1943+86T>G

Variant summary

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

The NM_001040458.3(ERAP1):​c.1943+86T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,260,756 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.897
• Publications: 14 publications found

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]

LOC124901031 (HGNC:):

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=-0.73).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1943+86T>G		intron_variant	Intron 13 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1943+86T>G		intron_variant	Intron 13 of 18	1	NM_001040458.3	ENSP00000406304.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1260756 Hom.: 0 Cov.: 17 AF XY: 0.00000158 AC XY: 1 AN XY: 633460

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29236

American (AMR) AF: 0.00 AC: 0 AN: 39498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24680

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37476

South Asian (SAS) AF: 0.00 AC: 0 AN: 79036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5396

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 943178

Other (OTH) AF: 0.00 AC: 0 AN: 53610

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.9
DANN	Benign	0.64
PhyloP100		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs469876; hg19: chr5-96121406;