rs27042

Variant names:

• chr5-96781236-G-A
• rs27042
• NM_001040458.3:c.2448-38C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-96781236-G-A
• chr5-96781236-G-C
• chr5-96781236-G-T

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.2448-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,592,212 control chromosomes in the GnomAD database, including 109,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11641 hom., cov: 29)
  • Exomes 𝑓: 0.36 (98355 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26
• Publications: 25 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-96781236-G-A is Benign according to our data. Variant chr5-96781236-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688424.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 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.2448-38C>T		intron	N/A	NP_001035548.1
	ERAP1	NM_001349244.2		c.2448-38C>T		intron	N/A	NP_001336173.1
	ERAP1	NM_016442.5		c.2448-38C>T		intron	N/A	NP_057526.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.2448-38C>T		intron	N/A	ENSP00000406304.2
	ERAP1	ENST00000296754.7	TSL:1	c.2448-38C>T		intron	N/A	ENSP00000296754.3
	ERAP1	ENST00000512852.1	TSL:3	c.-57C>T		upstream_gene	N/A	ENSP00000425381.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58207 AN: 150544 Hom.: 11624 Cov.: 29

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.384

GnomAD2 exomes AF: 0.358 AC: 89127 AN: 249052 AF XY: 0.369

Gnomad AFR exome AF: 0.484

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.254

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.365 AC: 525855 AN: 1441550 Hom.: 98355 Cov.: 27 AF XY: 0.370 AC XY: 265549 AN XY: 718326

African (AFR) AF: 0.476 AC: 15690 AN: 32946

American (AMR) AF: 0.238 AC: 10628 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 11062 AN: 25954

East Asian (EAS) AF: 0.290 AC: 11471 AN: 39524

South Asian (SAS) AF: 0.476 AC: 40697 AN: 85490

European-Finnish (FIN) AF: 0.306 AC: 16298 AN: 53186

Middle Eastern (MID) AF: 0.427 AC: 2438 AN: 5710

European-Non Finnish (NFE) AF: 0.361 AC: 395157 AN: 1094548

Other (OTH) AF: 0.376 AC: 22414 AN: 59620

GnomAD4 genome AF: 0.387 AC: 58265 AN: 150662 Hom.: 11641 Cov.: 29 AF XY: 0.384 AC XY: 28240 AN XY: 73480

African (AFR) AF: 0.475 AC: 19414 AN: 40844

American (AMR) AF: 0.299 AC: 4505 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1445 AN: 5112

South Asian (SAS) AF: 0.483 AC: 2292 AN: 4748

European-Finnish (FIN) AF: 0.292 AC: 3017 AN: 10344

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24718 AN: 67780

Other (OTH) AF: 0.387 AC: 807 AN: 2086

Alfa AF: 0.374 Hom.: 13310

Bravo AF: 0.384

Asia WGS AF: 0.395 AC: 1372 AN: 3476

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	-0.81
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-1.3
PromoterAI		0.056	Neutral
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: rs27042; hg19: chr5-96116940; COSMIC: COSV57089350; COSMIC: COSV57089350;