NM_002119.4:c.82+473C>A

Variant names:

• chr6-33008982-G-T
• rs86567
• NM_002119.4:c.82+473C>A

Variant summary

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

The NM_002119.4(HLA-DOA):​c.82+473C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,942 control chromosomes in the GnomAD database, including 29,621 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 0.62 (29621 hom., cov: 31)
• Consequence: HLA-DOA NM_002119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 36 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.82+473C>A		intron_variant	Intron 1 of 4	ENST00000229829.7	NP_002110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOA	ENST00000229829.7	c.82+473C>A		intron_variant	Intron 1 of 4	6	NM_002119.4	ENSP00000229829.3
HLA-DOA	ENST00000374813.1	c.82+473C>A		intron_variant	Intron 1 of 2	6		ENSP00000363946.1
HLA-DOA	ENST00000467465.1	n.128+473C>A		intron_variant	Intron 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94008 AN: 151824 Hom.: 29592 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.619 AC: 94082 AN: 151942 Hom.: 29621 Cov.: 31 AF XY: 0.622 AC XY: 46172 AN XY: 74278

African (AFR) AF: 0.704 AC: 29138 AN: 41412

American (AMR) AF: 0.543 AC: 8304 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2864 AN: 3468

East Asian (EAS) AF: 0.560 AC: 2888 AN: 5158

South Asian (SAS) AF: 0.766 AC: 3684 AN: 4808

European-Finnish (FIN) AF: 0.608 AC: 6418 AN: 10556

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38764 AN: 67936

Other (OTH) AF: 0.660 AC: 1393 AN: 2112

Alfa AF: 0.587 Hom.: 108267

Bravo AF: 0.613

Asia WGS AF: 0.710 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs86567; hg19: chr6-32976759;