XM_011543484.3:c.-451+12268G>T

Variant names:

• chr5-96861018-C-A
• rs62376445
• XM_011543484.3:c.-451+12268G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The XM_011543484.3(ERAP1):​c.-451+12268G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 151,710 control chromosomes in the GnomAD database, including 87 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 0.026 (87 hom., cov: 32)
• Consequence: ERAP1 XM_011543484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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]

ENSG00000247121 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0257 (3898/151710) while in subpopulation NFE AF= 0.0421 (2861/67950). AF 95% confidence interval is 0.0408. There are 87 homozygotes in gnomad4. There are 1741 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 87 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	XM_011543484.3	c.-451+12268G>T		intron_variant	Intron 3 of 23		XP_011541786.1
ERAP1	XM_011543485.3	c.-271+12268G>T		intron_variant	Intron 3 of 22		XP_011541787.1
ERAP1	XM_017009581.2	c.-455+12268G>T		intron_variant	Intron 2 of 22		XP_016865070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000247121	ENST00000501338.5	n.1781+12268G>T		intron_variant	Intron 2 of 3	2
ENSG00000247121	ENST00000502262.4	n.252+12268G>T		intron_variant	Intron 2 of 3	5
ENSG00000247121	ENST00000504056.5	n.191+12268G>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3899 AN: 151594 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.00665

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0257 AC: 3898 AN: 151710 Hom.: 87 Cov.: 32 AF XY: 0.0235 AC XY: 1741 AN XY: 74102

Gnomad4 AFR AF: 0.00663

Gnomad4 AMR AF: 0.0176

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0204

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0421

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.00987 Hom.: 9

Bravo AF: 0.0264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62376445; hg19: chr5-96196721;