rs9272143

Variant summary

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

The ENST00000422863.1(HLA-DQA1):​c.-39+117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,194 control chromosomes in the GnomAD database, including 18,132 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 0.49 ( 18132 hom., cov: 30)
Failed GnomAD Quality Control

Consequence

HLA-DQA1
ENST00000422863.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0400

Publications

46 publications found
Variant links:
Genes affected
HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

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=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 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-DQA1ENST00000422863.1 linkc.-39+117T>C intron_variant Intron 3 of 3 6 ENSP00000405797.1 F6UB03

Frequencies

GnomAD3 genomes
AF:
0.487
AC:
73501
AN:
151076
Hom.:
18119
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.463
Gnomad AMI
AF:
0.479
Gnomad AMR
AF:
0.482
Gnomad ASJ
AF:
0.577
Gnomad EAS
AF:
0.359
Gnomad SAS
AF:
0.456
Gnomad FIN
AF:
0.502
Gnomad MID
AF:
0.611
Gnomad NFE
AF:
0.505
Gnomad OTH
AF:
0.529
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.487
AC:
73557
AN:
151194
Hom.:
18132
Cov.:
30
AF XY:
0.485
AC XY:
35773
AN XY:
73830
show subpopulations
African (AFR)
AF:
0.463
AC:
19087
AN:
41196
American (AMR)
AF:
0.481
AC:
7309
AN:
15196
Ashkenazi Jewish (ASJ)
AF:
0.577
AC:
1993
AN:
3456
East Asian (EAS)
AF:
0.359
AC:
1850
AN:
5158
South Asian (SAS)
AF:
0.458
AC:
2187
AN:
4776
European-Finnish (FIN)
AF:
0.502
AC:
5255
AN:
10460
Middle Eastern (MID)
AF:
0.616
AC:
180
AN:
292
European-Non Finnish (NFE)
AF:
0.505
AC:
34159
AN:
67660
Other (OTH)
AF:
0.527
AC:
1101
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
1620
3240
4861
6481
8101
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
662
1324
1986
2648
3310
<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:
0.462
Hom.:
8219
Bravo
AF:
0.479
Asia WGS
AF:
0.398
AC:
1387
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
7.5
DANN
Benign
0.82
PhyloP100
0.040

Splicing

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

Publications

Other links and lift over

dbSNP: rs9272143; hg19: chr6-32600803; API