chr5-96788750-A-G

Variant names:

• chr5-96788750-A-G
• rs11743410
• NM_001040458.3:c.1525-65T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040458.3(ERAP1):​c.1525-65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,577,132 control chromosomes in the GnomAD database, including 11,321 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 0.092 (843 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10478 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1525-65T>C		intron_variant	Intron 10 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1525-65T>C		intron_variant	Intron 10 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.1525-65T>C		intron_variant	Intron 10 of 19	1		ENSP00000296754.3
ERAP1	ENST00000507859.1	n.188-65T>C		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13938 AN: 152066 Hom.: 844 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.117 AC: 166595 AN: 1424948 Hom.: 10478 AF XY: 0.117 AC XY: 82640 AN XY: 707056

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.0800

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.000755

Gnomad4 SAS exome AF: 0.0825

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0916 AC: 13934 AN: 152184 Hom.: 843 Cov.: 32 AF XY: 0.0916 AC XY: 6812 AN XY: 74402

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0841

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.119

Alfa AF: 0.106 Hom.: 114

Bravo AF: 0.0876

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.54

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: rs11743410; hg19: chr5-96124453;