5-96785702-A-G

Position:

• chr5-96785702-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001040458.3(ERAP1):​c.1943+86T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,410,578 control chromosomes in the GnomAD database, including 38,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3852 hom., cov: 33)
  • Exomes 𝑓: 0.23 (34235 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.897

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 5-96785702-A-G is Benign according to our data. Variant chr5-96785702-A-G is described in ClinVar as [Benign]. Clinvar id is 2688459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1943+86T>C		intron_variant		ENST00000443439.7	NP_001035548.1
LOC124901031	XR_007058877.1	n.1307A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1943+86T>C		intron_variant		1	NM_001040458.3	ENSP00000406304	P1
	ENST00000512856.1	n.722-26A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34000 AN: 152066 Hom.: 3850 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.232 AC: 291705 AN: 1258394 Hom.: 34235 Cov.: 17 AF XY: 0.233 AC XY: 147063 AN XY: 632330

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.224 AC: 34022 AN: 152184 Hom.: 3852 Cov.: 33 AF XY: 0.222 AC XY: 16552 AN XY: 74406

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.225

Alfa AF: 0.239 Hom.: 699

Bravo AF: 0.216

Asia WGS AF: 0.267 AC: 928 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.1
DANN	Benign	0.63

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: rs469876; hg19: chr5-96121406;