rs10515248

Variant names:

• chr5-96776301-C-T
• rs10515248
• NM_001040458.3:c.*95G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001040458.3(ERAP1):​c.*95G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,544,294 control chromosomes in the GnomAD database, including 10,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (827 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10084 hom.)
• Consequence: ERAP1 NM_001040458.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0390
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-96776301-C-T is Benign according to our data. Variant chr5-96776301-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	NM_001040458.3	MANE Select	c.*95G>A		3_prime_UTR	Exon 19 of 19	NP_001035548.1
	ERAP1	NM_001198541.3		c.*95G>A		3_prime_UTR	Exon 19 of 19	NP_001185470.1
	ERAP1	NM_001349244.2		c.2818+103G>A		intron	N/A	NP_001336173.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.*95G>A		3_prime_UTR	Exon 19 of 19	ENSP00000406304.2
	ERAP1	ENST00000296754.7	TSL:1	c.2818+103G>A		intron	N/A	ENSP00000296754.3
	CAST	ENST00000510098.1	TSL:1	n.*351-567C>T		intron	N/A	ENSP00000427195.1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13823 AN: 152050 Hom.: 828 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.116 AC: 161975 AN: 1392126 Hom.: 10084 Cov.: 34 AF XY: 0.116 AC XY: 79859 AN XY: 685950

African (AFR) AF: 0.0192 AC: 597 AN: 31104

American (AMR) AF: 0.0784 AC: 2753 AN: 35136

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2592 AN: 22532

East Asian (EAS) AF: 0.000796 AC: 31 AN: 38948

South Asian (SAS) AF: 0.0799 AC: 5995 AN: 74990

European-Finnish (FIN) AF: 0.118 AC: 5327 AN: 45132

Middle Eastern (MID) AF: 0.114 AC: 618 AN: 5436

European-Non Finnish (NFE) AF: 0.127 AC: 137650 AN: 1081328

Other (OTH) AF: 0.111 AC: 6412 AN: 57520

GnomAD4 genome AF: 0.0908 AC: 13819 AN: 152168 Hom.: 827 Cov.: 32 AF XY: 0.0910 AC XY: 6771 AN XY: 74376

African (AFR) AF: 0.0220 AC: 912 AN: 41536

American (AMR) AF: 0.101 AC: 1537 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0832 AC: 400 AN: 4810

European-Finnish (FIN) AF: 0.126 AC: 1337 AN: 10584

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8791 AN: 67996

Other (OTH) AF: 0.117 AC: 247 AN: 2108

Alfa AF: 0.121 Hom.: 1976

Bravo AF: 0.0865

Asia WGS AF: 0.0370 AC: 131 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		-0.039
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: rs10515248; hg19: chr5-96112005; COSMIC: COSV57086928; COSMIC: COSV57086928;