5-96786556-T-G

Variant names:

• chr5-96786556-T-G
• rs30379
• NM_001040458.3:c.1680-7A>C

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.1680-7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,581,154 control chromosomes in the GnomAD database, including 328,368 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29766 hom., cov: 33)
  • Exomes 𝑓: 0.64 (298602 hom.)
• Consequence: ERAP1 NM_001040458.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001424
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.300
• Publications: 17 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-96786556-T-G is Benign according to our data. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-96786556-T-G is described in CliVar as Benign. Clinvar id is 2688357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1680-7A>C		splice_region_variant, 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.1680-7A>C		splice_region_variant, intron_variant	Intron 11 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.1680-7A>C		splice_region_variant, intron_variant	Intron 11 of 19	1		ENSP00000296754.3
ERAP1	ENST00000507859.1	n.343-7A>C		splice_region_variant, intron_variant	Intron 3 of 4	2
ERAP1	ENST00000514604.5	n.104-7A>C		splice_region_variant, intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94748 AN: 151850 Hom.: 29736 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.567

GnomAD2 exomes AF: 0.620 AC: 154865 AN: 249884 AF XY: 0.620

Gnomad AFR exome AF: 0.607

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.553

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.653

Gnomad NFE exome AF: 0.654

Gnomad OTH exome AF: 0.615

GnomAD4 exome AF: 0.644 AC: 920909 AN: 1429186 Hom.: 298602 Cov.: 26 AF XY: 0.643 AC XY: 458538 AN XY: 712986

African (AFR) AF: 0.596 AC: 19633 AN: 32942

American (AMR) AF: 0.608 AC: 27153 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 14392 AN: 25954

East Asian (EAS) AF: 0.515 AC: 20358 AN: 39548

South Asian (SAS) AF: 0.586 AC: 50231 AN: 85668

European-Finnish (FIN) AF: 0.653 AC: 34802 AN: 53336

Middle Eastern (MID) AF: 0.590 AC: 3167 AN: 5364

European-Non Finnish (NFE) AF: 0.660 AC: 714271 AN: 1082436

Other (OTH) AF: 0.622 AC: 36902 AN: 59306

GnomAD4 genome AF: 0.624 AC: 94824 AN: 151968 Hom.: 29766 Cov.: 33 AF XY: 0.621 AC XY: 46146 AN XY: 74296

African (AFR) AF: 0.603 AC: 25001 AN: 41430

American (AMR) AF: 0.596 AC: 9108 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3466

East Asian (EAS) AF: 0.514 AC: 2659 AN: 5176

South Asian (SAS) AF: 0.587 AC: 2824 AN: 4814

European-Finnish (FIN) AF: 0.646 AC: 6811 AN: 10538

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44726 AN: 67948

Other (OTH) AF: 0.569 AC: 1197 AN: 2104

Alfa AF: 0.640 Hom.: 13669

Bravo AF: 0.616

Asia WGS AF: 0.593 AC: 2063 AN: 3478

EpiCase AF: 0.652

EpiControl AF: 0.641

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.64
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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: rs30379; hg19: chr5-96122260; COSMIC: COSV57085263; COSMIC: COSV57085263;