rs149078

Variant names:

• chr5-96779489-G-A
• rs149078
• ENST00000510098.1:n.*605G>A

Variant summary

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

The ENST00000510098.1(CAST):​n.*605G>A 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 0.334 in 151,994 control chromosomes in the GnomAD database, including 8,882 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 0.33 (8882 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CAST ENST00000510098.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 12 publications found

Genes affected

CAST (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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.2670+934C>T		intron_variant	Intron 18 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.2670+934C>T		intron_variant	Intron 18 of 18	1	NM_001040458.3	ENSP00000406304.2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50768 AN: 151872 Hom.: 8867 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.334 AC: 50830 AN: 151992 Hom.: 8882 Cov.: 32 AF XY: 0.334 AC XY: 24797 AN XY: 74302

African (AFR) AF: 0.436 AC: 18057 AN: 41434

American (AMR) AF: 0.320 AC: 4896 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3468

East Asian (EAS) AF: 0.288 AC: 1486 AN: 5162

South Asian (SAS) AF: 0.330 AC: 1590 AN: 4816

European-Finnish (FIN) AF: 0.244 AC: 2572 AN: 10560

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19929 AN: 67960

Other (OTH) AF: 0.338 AC: 711 AN: 2104

Alfa AF: 0.307 Hom.: 12270

Bravo AF: 0.340

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.62
PhyloP100		-0.21
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: rs149078; hg19: chr5-96115193;