rs13154629

Positions:

• chr5-96786754-C-T

Variant summary

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

The NM_001040458.3(ERAP1):​c.1680-205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 549,760 control chromosomes in the GnomAD database, including 8,366 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 0.16 (2259 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6107 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1680-205G>A		intron_variant		ENST00000443439.7	NP_001035548.1
LOC124901031	XR_007058877.1	n.2359C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1680-205G>A		intron_variant		1	NM_001040458.3	ENSP00000406304	P1
ERAP1	ENST00000296754.7	c.1680-205G>A		intron_variant		1		ENSP00000296754
ERAP1	ENST00000514604.5	n.7G>A		non_coding_transcript_exon_variant	1/6	5
ERAP1	ENST00000507859.1	n.343-205G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24534 AN: 151984 Hom.: 2257 Cov.: 32

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0463

Gnomad SAS AF: 0.0905

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.165 AC: 65801 AN: 397658 Hom.: 6107 Cov.: 2 AF XY: 0.161 AC XY: 34216 AN XY: 212056

Gnomad4 AFR exome AF: 0.0908

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0421

Gnomad4 SAS exome AF: 0.0950

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.161 AC: 24550 AN: 152102 Hom.: 2259 Cov.: 32 AF XY: 0.159 AC XY: 11818 AN XY: 74330

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0466

Gnomad4 SAS AF: 0.0914

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.136

Alfa AF: 0.192 Hom.: 1348

Bravo AF: 0.154

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs13154629; hg19: chr5-96122458;