5-96861018-C-T

Variant names:

• chr5-96861018-C-T
• rs62376445
• ENST00000501338.6:n.1781+12268G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000501338.6(ENSG00000247121):​n.1781+12268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 151,716 control chromosomes in the GnomAD database, including 12 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 0.010 (12 hom., cov: 32)
• Consequence: ENSG00000247121 ENST00000501338.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 3 publications found

Genes affected

ENSG00000247121 (HGNC:):

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000247121	ENST00000501338.6	n.1781+12268G>A		intron_variant	Intron 2 of 3	2
ENSG00000247121	ENST00000502262.4	n.252+12268G>A		intron_variant	Intron 2 of 3	5
ENSG00000247121	ENST00000504056.5	n.191+12268G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1554 AN: 151600 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00238

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.00724

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00976

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.00480

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

GnomAD4 genome AF: 0.0102 AC: 1554 AN: 151716 Hom.: 12 Cov.: 32 AF XY: 0.0104 AC XY: 774 AN XY: 74102

African (AFR) AF: 0.00237 AC: 98 AN: 41330

American (AMR) AF: 0.00723 AC: 110 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00664 AC: 23 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00978 AC: 47 AN: 4808

European-Finnish (FIN) AF: 0.0250 AC: 262 AN: 10470

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0142 AC: 964 AN: 67956

Other (OTH) AF: 0.00475 AC: 10 AN: 2106

Alfa AF: 0.00741 Hom.: 9

Bravo AF: 0.00825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.60
PhyloP100		-0.078

Splicing

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

Other links and lift over

dbSNP: rs62376445; hg19: chr5-96196721;