NM_001040458.3:c.*729C>T

Variant names:

• chr5-96775667-G-A
• rs13160562
• NM_001040458.3:c.*729C>T

Variant summary

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

The NM_001040458.3(ERAP1):​c.*729C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 241,920 control chromosomes in the GnomAD database, including 8,782 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 0.22 (4344 hom., cov: 33)
  • Exomes 𝑓: 0.30 (4438 hom.)
• Consequence: ERAP1 NM_001040458.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 48 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040458.3. 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.*729C>T		3_prime_UTR	Exon 19 of 19	NP_001035548.1
	ERAP1	NM_001198541.3		c.*729C>T		3_prime_UTR	Exon 19 of 19	NP_001185470.1
	ERAP1	NM_001349244.2		c.2818+737C>T		intron	N/A	NP_001336173.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.*729C>T		3_prime_UTR	Exon 19 of 19	ENSP00000406304.2
	ERAP1	ENST00000296754.7	TSL:1	c.2818+737C>T		intron	N/A	ENSP00000296754.3
	CAST	ENST00000510098.1	TSL:1	n.*351-1201G>A		intron	N/A	ENSP00000427195.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34189 AN: 152058 Hom.: 4341 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.302 AC: 27135 AN: 89744 Hom.: 4438 Cov.: 5 AF XY: 0.301 AC XY: 13117 AN XY: 43522

African (AFR) AF: 0.118 AC: 188 AN: 1594

American (AMR) AF: 0.127 AC: 14 AN: 110

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 151 AN: 546

East Asian (EAS) AF: 0.0455 AC: 18 AN: 396

South Asian (SAS) AF: 0.177 AC: 293 AN: 1656

European-Finnish (FIN) AF: 0.423 AC: 11 AN: 26

Middle Eastern (MID) AF: 0.289 AC: 59 AN: 204

European-Non Finnish (NFE) AF: 0.312 AC: 25636 AN: 82282

Other (OTH) AF: 0.261 AC: 765 AN: 2930

GnomAD4 genome AF: 0.225 AC: 34200 AN: 152176 Hom.: 4344 Cov.: 33 AF XY: 0.220 AC XY: 16354 AN XY: 74408

African (AFR) AF: 0.125 AC: 5206 AN: 41530

American (AMR) AF: 0.186 AC: 2849 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3466

East Asian (EAS) AF: 0.0480 AC: 249 AN: 5188

South Asian (SAS) AF: 0.158 AC: 761 AN: 4828

European-Finnish (FIN) AF: 0.277 AC: 2930 AN: 10592

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.303 AC: 20618 AN: 67960

Other (OTH) AF: 0.211 AC: 445 AN: 2112

Alfa AF: 0.251 Hom.: 6298

Bravo AF: 0.214

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.6
DANN	Benign	0.80
PhyloP100		-0.12
Mutation Taster		=98/2	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: rs13160562; hg19: chr5-96111371;