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GeneBe

6-33008236-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002119.4(HLA-DOA):c.108C>T(p.Pro36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,612,572 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 30 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 39 hom. )

Consequence

HLA-DOA
NM_002119.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05
Variant links:
Genes affected
HLA-DOA (HGNC:4936): (major histocompatibility complex, class II, DO alpha) HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-33008236-G-A is Benign according to our data. Variant chr6-33008236-G-A is described in ClinVar as [Benign]. Clinvar id is 768080.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.05 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1872/152298) while in subpopulation AFR AF= 0.0423 (1758/41570). AF 95% confidence interval is 0.0406. There are 30 homozygotes in gnomad4. There are 857 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 30 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HLA-DOANM_002119.4 linkuse as main transcriptc.108C>T p.Pro36= synonymous_variant 2/5 ENST00000229829.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HLA-DOAENST00000229829.7 linkuse as main transcriptc.108C>T p.Pro36= synonymous_variant 2/5 NM_002119.4 P1
HLA-DOAENST00000374813.1 linkuse as main transcriptc.83-142C>T intron_variant
HLA-DOAENST00000467465.1 linkuse as main transcriptn.297C>T non_coding_transcript_exon_variant 2/2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0123
AC:
1870
AN:
152178
Hom.:
30
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0424
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00373
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000470
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00326
AC:
800
AN:
245624
Hom.:
20
AF XY:
0.00223
AC XY:
299
AN XY:
133964
show subpopulations
Gnomad AFR exome
AF:
0.0426
Gnomad AMR exome
AF:
0.00253
Gnomad ASJ exome
AF:
0.000302
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000231
Gnomad FIN exome
AF:
0.0000927
Gnomad NFE exome
AF:
0.000500
Gnomad OTH exome
AF:
0.000825
GnomAD4 exome
AF:
0.00160
AC:
2338
AN:
1460274
Hom.:
39
Cov.:
33
AF XY:
0.00138
AC XY:
1004
AN XY:
726468
show subpopulations
Gnomad4 AFR exome
AF:
0.0448
Gnomad4 AMR exome
AF:
0.00293
Gnomad4 ASJ exome
AF:
0.000344
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.0000766
Gnomad4 NFE exome
AF:
0.000431
Gnomad4 OTH exome
AF:
0.00306
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0123
AC:
1872
AN:
152298
Hom.:
30
Cov.:
32
AF XY:
0.0115
AC XY:
857
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0423
Gnomad4 AMR
AF:
0.00372
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000470
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00720
Hom.:
5
Bravo
AF:
0.0141
EpiCase
AF:
0.000818
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
7.4
Dann
Benign
0.75

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs78635760; hg19: chr6-32976013; API