chr6-32666786-C-T

Variant summary

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

The ENST00000399084.5(HLA-DQB1):​c.-63-116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 211,278 control chromosomes in the GnomAD database, including 1,033 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 0.22 ( 958 hom., cov: 8)
Exomes 𝑓: 0.023 ( 75 hom. )

Consequence

HLA-DQB1
ENST00000399084.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.13

Publications

8 publications found
Variant links:
Genes affected
HLA-DQB1 (HGNC:4944): (major histocompatibility complex, class II, DQ beta 1) HLA-DQB1 belongs to the HLA class II beta chain paralogs. This 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 beta chain is approximately 26-28 kDa and it contains six exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

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=-0.79).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HLA-DQB1NM_002123.5 linkc.-179G>A upstream_gene_variant ENST00000434651.7 NP_002114.3 P01920Q5Y7D6Q5Y7A9
HLA-DQB1NM_001243961.2 linkc.-179G>A upstream_gene_variant NP_001230890.1 Q5SU54

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HLA-DQB1ENST00000434651.7 linkc.-179G>A upstream_gene_variant 6 NM_002123.5 ENSP00000407332.2 Q5Y7D6
HLA-DQB1ENST00000374943.8 linkc.-179G>A upstream_gene_variant 6 ENSP00000364080.4 Q5SU54

Frequencies

GnomAD3 genomes
AF:
0.216
AC:
15164
AN:
70280
Hom.:
958
Cov.:
8
show subpopulations
Gnomad AFR
AF:
0.217
Gnomad AMI
AF:
0.150
Gnomad AMR
AF:
0.179
Gnomad ASJ
AF:
0.168
Gnomad EAS
AF:
0.0988
Gnomad SAS
AF:
0.200
Gnomad FIN
AF:
0.150
Gnomad MID
AF:
0.318
Gnomad NFE
AF:
0.243
Gnomad OTH
AF:
0.213
GnomAD4 exome
AF:
0.0234
AC:
3294
AN:
140942
Hom.:
75
AF XY:
0.0241
AC XY:
1796
AN XY:
74446
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0205
AC:
77
AN:
3760
American (AMR)
AF:
0.00996
AC:
31
AN:
3114
Ashkenazi Jewish (ASJ)
AF:
0.0110
AC:
39
AN:
3560
East Asian (EAS)
AF:
0.00159
AC:
14
AN:
8786
South Asian (SAS)
AF:
0.0364
AC:
425
AN:
11666
European-Finnish (FIN)
AF:
0.0110
AC:
148
AN:
13468
Middle Eastern (MID)
AF:
0.0710
AC:
50
AN:
704
European-Non Finnish (NFE)
AF:
0.0262
AC:
2295
AN:
87606
Other (OTH)
AF:
0.0260
AC:
215
AN:
8278
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.327
Heterozygous variant carriers
0
206
411
617
822
1028
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.216
AC:
15169
AN:
70336
Hom.:
958
Cov.:
8
AF XY:
0.207
AC XY:
7117
AN XY:
34406
show subpopulations
African (AFR)
AF:
0.217
AC:
4302
AN:
19828
American (AMR)
AF:
0.179
AC:
997
AN:
5568
Ashkenazi Jewish (ASJ)
AF:
0.168
AC:
187
AN:
1112
East Asian (EAS)
AF:
0.0983
AC:
226
AN:
2298
South Asian (SAS)
AF:
0.200
AC:
505
AN:
2522
European-Finnish (FIN)
AF:
0.150
AC:
749
AN:
4980
Middle Eastern (MID)
AF:
0.321
AC:
34
AN:
106
European-Non Finnish (NFE)
AF:
0.243
AC:
7932
AN:
32684
Other (OTH)
AF:
0.207
AC:
185
AN:
892
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.421
Heterozygous variant carriers
0
499
998
1498
1997
2496
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
176
352
528
704
880
<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:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
3.4
DANN
Benign
0.73
PhyloP100
-2.1
PromoterAI
-0.23
Neutral
Mutation Taster
=100/0
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs78202368; hg19: chr6-32634563; API