rs1044429

Positions:

• chr6-33004865-C-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.*1973G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,274 control chromosomes in the GnomAD database, including 1,439 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 0.12 (1438 hom., cov: 32)
  • Exomes 𝑓: 0.089 (1 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.*1973G>A		3_prime_UTR_variant	5/5	ENST00000229829.7	NP_002110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DOA	ENST00000229829	c.*1973G>A		3_prime_UTR_variant	5/5		NM_002119.4	ENSP00000229829.3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19008 AN: 152100 Hom.: 1439 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0893 AC: 5 AN: 56 Hom.: 1 Cov.: 0 AF XY: 0.0435 AC XY: 2 AN XY: 46

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0833

GnomAD4 genome AF: 0.125 AC: 19022 AN: 152218 Hom.: 1438 Cov.: 32 AF XY: 0.130 AC XY: 9651 AN XY: 74414

Gnomad4 AFR AF: 0.0571

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.151

Alfa AF: 0.153 Hom.: 3820

Bravo AF: 0.122

Asia WGS AF: 0.267 AC: 929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.47

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: rs1044429; hg19: chr6-32972642;