chr5-96777338-A-G

Variant names:

• chr5-96777338-A-G
• rs27639
• NM_001040458.3:c.2671-787T>C

Variant summary

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

The NM_001040458.3(ERAP1):​c.2671-787T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,174 control chromosomes in the GnomAD database, including 1,653 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 0.13 (1653 hom., cov: 32)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 3 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.2671-787T>C		intron_variant	Intron 18 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.2671-787T>C		intron_variant	Intron 18 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.2671-787T>C		intron_variant	Intron 18 of 19	1		ENSP00000296754.3
CAST	ENST00000510098.1	n.*437+384A>G		intron_variant	Intron 11 of 11	1		ENSP00000427195.1
ERAP1	ENST00000512852.1	c.205-787T>C		intron_variant	Intron 2 of 3	3		ENSP00000425381.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19373 AN: 152056 Hom.: 1647 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.127 AC: 19383 AN: 152174 Hom.: 1653 Cov.: 32 AF XY: 0.133 AC XY: 9895 AN XY: 74394

African (AFR) AF: 0.0565 AC: 2345 AN: 41534

American (AMR) AF: 0.247 AC: 3778 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1302 AN: 5168

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4820

European-Finnish (FIN) AF: 0.154 AC: 1634 AN: 10578

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8460 AN: 67998

Other (OTH) AF: 0.116 AC: 245 AN: 2112

Alfa AF: 0.131 Hom.: 2070

Bravo AF: 0.133

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.2
DANN	Benign	0.64
PhyloP100		0.63
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: rs27639; hg19: chr5-96113042; COSMIC: COSV57086318; COSMIC: COSV57086318;