rs2284191

Positions:

• chr6-33008877-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002119.4(HLA-DOA):​c.82+578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,144 control chromosomes in the GnomAD database, including 601 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 0.076 (601 hom., cov: 32)
• Consequence: HLA-DOA NM_002119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.82+578C>T		intron_variant		ENST00000229829.7	NP_002110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DOA	ENST00000229829.7	c.82+578C>T		intron_variant			NM_002119.4	ENSP00000229829	P1
HLA-DOA	ENST00000374813.1	c.82+578C>T		intron_variant				ENSP00000363946
HLA-DOA	ENST00000467465.1	n.129-473C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11631 AN: 152026 Hom.: 600 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0765 AC: 11633 AN: 152144 Hom.: 601 Cov.: 32 AF XY: 0.0811 AC XY: 6032 AN XY: 74358

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.0873

Gnomad4 OTH AF: 0.0648

Alfa AF: 0.0848 Hom.: 1160

Bravo AF: 0.0639

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs2284191; hg19: chr6-32976654;