ENST00000706902.1:n.*816G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.464

Publications

14 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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-AENST00000706902.1 linkn.*816G>T non_coding_transcript_exon_variant Exon 10 of 10 ENSP00000516613.1 A0A9L9PY26
HLA-AENST00000706904.1 linkc.*902G>T 3_prime_UTR_variant Exon 9 of 9 ENSP00000516615.1 A0A9L9PY26
HLA-AENST00000706902.1 linkn.*816G>T 3_prime_UTR_variant Exon 10 of 10 ENSP00000516613.1 A0A9L9PY26

Frequencies

GnomAD3 genomes
AF:
0.170
AC:
25869
AN:
151916
Hom.:
2635
Cov.:
34
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.484
Heterozygous variant carriers
0
980
1960
2939
3919
4899
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
312
624
936
1248
1560
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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

Publications

Other links and lift over

dbSNP: rs1632882; hg19: chr6-29916368; API