NM_001040458.3:c.1680-205G>A

Variant names:

• chr5-96786754-C-T
• rs13154629
• NM_001040458.3:c.1680-205G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1680-205G>A		intron_variant	Intron 11 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1680-205G>A		intron_variant	Intron 11 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.1680-205G>A		intron_variant	Intron 11 of 19	1		ENSP00000296754.3
ERAP1	ENST00000514604.5	n.7G>A		non_coding_transcript_exon_variant	Exon 1 of 6	5
ERAP1	ENST00000507859.1	n.343-205G>A		intron_variant	Intron 3 of 4	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

African (AFR) AF: 0.0908 AC: 1018 AN: 11206

American (AMR) AF: 0.108 AC: 1809 AN: 16812

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 1426 AN: 11958

East Asian (EAS) AF: 0.0421 AC: 1142 AN: 27128

South Asian (SAS) AF: 0.0950 AC: 4167 AN: 43882

European-Finnish (FIN) AF: 0.178 AC: 4340 AN: 24366

Middle Eastern (MID) AF: 0.112 AC: 192 AN: 1720

European-Non Finnish (NFE) AF: 0.202 AC: 48026 AN: 237884

Other (OTH) AF: 0.162 AC: 3681 AN: 22702

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

African (AFR) AF: 0.0948 AC: 3935 AN: 41510

American (AMR) AF: 0.139 AC: 2122 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3464

East Asian (EAS) AF: 0.0466 AC: 241 AN: 5176

South Asian (SAS) AF: 0.0914 AC: 440 AN: 4814

European-Finnish (FIN) AF: 0.204 AC: 2150 AN: 10560

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14802 AN: 67974

Other (OTH) AF: 0.136 AC: 288 AN: 2110

Alfa AF: 0.192 Hom.: 1513

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
PhyloP100		0.085
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: rs13154629; hg19: chr5-96122458;