6-33008982-G-T

Position:

• chr6-33008982-G-T

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+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

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=-0.84).
• 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/exons	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.82+473C>A		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+473C>A		intron_variant			NM_002119.4	ENSP00000229829	P1
HLA-DOA	ENST00000374813.1	c.82+473C>A		intron_variant				ENSP00000363946
HLA-DOA	ENST00000467465.1	n.128+473C>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.660

Alfa AF: 0.585 Hom.: 48200

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

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: rs86567; hg19: chr6-32976759;