5-96815208-C-T

Variant names:

• chr5-96815208-C-T
• rs34753
• ENST00000723517.1:n.1661C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000723517.1(ENSG00000294423):​n.1661C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,022 control chromosomes in the GnomAD database, including 33,600 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 0.66 (33600 hom., cov: 31)
• Consequence: ENSG00000294423 ENST00000723517.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 12 publications found

Genes affected

ENSG00000294423 (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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901033	XR_007058879.1	n.2439C>T		non_coding_transcript_exon_variant	Exon 3 of 3
ERAP1	XM_011543484.3	c.-266-898G>A		intron_variant	Intron 4 of 23		XP_011541786.1
ERAP1	XM_011543485.3	c.-270-898G>A		intron_variant	Intron 3 of 22		XP_011541787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000294423	ENST00000723517.1	n.1661C>T		non_coding_transcript_exon_variant	Exon 4 of 4
ENSG00000247121	ENST00000501338.6	n.1963-898G>A		intron_variant	Intron 3 of 3	2
ENSG00000247121	ENST00000502262.4	n.434-898G>A		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100249 AN: 151902 Hom.: 33575 Cov.: 31

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.660 AC: 100335 AN: 152022 Hom.: 33600 Cov.: 31 AF XY: 0.656 AC XY: 48765 AN XY: 74284

African (AFR) AF: 0.605 AC: 25079 AN: 41436

American (AMR) AF: 0.607 AC: 9272 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1967 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2392 AN: 5166

South Asian (SAS) AF: 0.558 AC: 2687 AN: 4814

European-Finnish (FIN) AF: 0.726 AC: 7664 AN: 10552

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.723 AC: 49181 AN: 67990

Other (OTH) AF: 0.651 AC: 1372 AN: 2106

Alfa AF: 0.692 Hom.: 18757

Bravo AF: 0.648

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.25
DANN	Benign	0.61
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs34753; hg19: chr5-96150911;