rs249957

chr5-96785338-T-C

Variant summary

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

The NM_001040458.3(ERAP1):c.1943+450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 204,674 control chromosomes in the GnomAD database, including 339 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 0.045 (212 hom., cov: 32)
  • Exomes 𝑓: 0.052 (127 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3	c.1943+450A>G		intron_variant		ENST00000443439.7
LOC124901031	XR_007058877.1	n.990-47T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.1943+450A>G		intron_variant		1	NM_001040458.3	P1
	ENST00000512856.1	n.562T>C		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6925 AN: 152168 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0523 AC: 2738 AN: 52386 Hom.: 127 Cov.: 0 AF XY: 0.0571 AC XY: 1568 AN XY: 27454

Gnomad4 AFR exome AF: 0.00960

Gnomad4 AMR exome AF: 0.0377

Gnomad4 ASJ exome AF: 0.0833

Gnomad4 EAS exome AF: 0.000323

Gnomad4 SAS exome AF: 0.0873

Gnomad4 FIN exome AF: 0.0286

Gnomad4 NFE exome AF: 0.0533

Gnomad4 OTH exome AF: 0.0474

GnomAD4 genome AF: 0.0455 AC: 6928 AN: 152288 Hom.: 212 Cov.: 32 AF XY: 0.0447 AC XY: 3330 AN XY: 74476

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0347

Gnomad4 NFE AF: 0.0646

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0569 Hom.: 42

Bravo AF: 0.0423

Asia WGS AF: 0.0360 AC: 124 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	11
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs249957; hg19: chr5-96121042; COSMIC: COSV57086346; COSMIC: COSV57086346;