ENST00000706902.1:n.*816G>T

Variant names:

• chr6-29948591-G-T
• rs1632882
• ENST00000706902.1:n.*816G>T

Variant summary

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

The ENST00000706902.1(HLA-A):​n.*816G>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 0.17 in 152,034 control chromosomes in the GnomAD database, including 2,637 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 0.17 (2637 hom., cov: 34)
• Consequence: HLA-A ENST00000706902.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464
• Publications: 14 publications found

Genes affected

HLA-A (HGNC:4931): (major histocompatibility complex, class I, A) HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen so that they can be recognized by cytotoxic T cells. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. More than 6000 HLA-A alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

POLR1HASP (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-A	ENST00000706902.1	n.*816G>T		non_coding_transcript_exon_variant	Exon 10 of 10			ENSP00000516613.1
HLA-A	ENST00000706904.1	c.*902G>T		3_prime_UTR_variant	Exon 9 of 9			ENSP00000516615.1
HLA-A	ENST00000706902.1	n.*816G>T		3_prime_UTR_variant	Exon 10 of 10			ENSP00000516613.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25869 AN: 151916 Hom.: 2635 Cov.: 34

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.170 AC: 25864 AN: 152034 Hom.: 2637 Cov.: 34 AF XY: 0.168 AC XY: 12461 AN XY: 74336

African (AFR) AF: 0.0861 AC: 3568 AN: 41446

American (AMR) AF: 0.117 AC: 1788 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3472

East Asian (EAS) AF: 0.283 AC: 1460 AN: 5166

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4816

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10590

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15124 AN: 67956

Other (OTH) AF: 0.161 AC: 341 AN: 2112

Alfa AF: 0.175 Hom.: 788

Bravo AF: 0.164

Asia WGS AF: 0.228 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.68
PhyloP100		0.46

Splicing

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

Other links and lift over

dbSNP: rs1632882; hg19: chr6-29916368;