chr5-96777250-A-G

Variant names:

• chr5-96777250-A-G
• rs27038
• NM_001040458.3:c.2671-699T>C

Variant summary

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

The NM_016442.5(ERAP1):​c.2671-699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,196 control chromosomes in the GnomAD database, including 51,103 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 0.82 (51103 hom., cov: 32)
• Consequence: ERAP1 NM_016442.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803
• Publications: 26 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]

CAST (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016442.5. 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_001040458.3	MANE Select	c.2671-699T>C		intron	N/A	NP_001035548.1
	ERAP1	NM_001349244.2		c.2671-699T>C		intron	N/A	NP_001336173.1
	ERAP1	NM_016442.5		c.2671-699T>C		intron	N/A	NP_057526.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.2671-699T>C		intron	N/A	ENSP00000406304.2
	ERAP1	ENST00000296754.7	TSL:1	c.2671-699T>C		intron	N/A	ENSP00000296754.3
	CAST	ENST00000510098.1	TSL:1	n.*437+296A>G		intron	N/A	ENSP00000427195.1

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124216 AN: 152076 Hom.: 51052 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.817 AC: 124318 AN: 152196 Hom.: 51103 Cov.: 32 AF XY: 0.817 AC XY: 60787 AN XY: 74402

African (AFR) AF: 0.760 AC: 31530 AN: 41510

American (AMR) AF: 0.876 AC: 13402 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2877 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3247 AN: 5176

South Asian (SAS) AF: 0.810 AC: 3911 AN: 4830

European-Finnish (FIN) AF: 0.813 AC: 8608 AN: 10584

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58001 AN: 68012

Other (OTH) AF: 0.815 AC: 1722 AN: 2112

Alfa AF: 0.844 Hom.: 55755

Bravo AF: 0.818

Asia WGS AF: 0.749 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.62
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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: rs27038; hg19: chr5-96112954;