rs592625

chr6-33004913-T-Cchr6-33004913-T-G

Variant summary

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

The NM_002119.4(HLA-DOA):c.*1925A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,260 control chromosomes in the GnomAD database, including 1,897 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 0.15 (1896 hom., cov: 32)
  • Exomes 𝑓: 0.29 (1 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DOA	NM_002119.4	c.*1925A>G		3_prime_UTR_variant	5/5	ENST00000229829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DOA	ENST00000229829.7	c.*1925A>G		3_prime_UTR_variant	5/5		NM_002119.4	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22672 AN: 152126 Hom.: 1894 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.286 AC: 4 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.375

GnomAD4 genome AF: 0.149 AC: 22693 AN: 152246 Hom.: 1896 Cov.: 32 AF XY: 0.153 AC XY: 11407 AN XY: 74446

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.181

Alfa AF: 0.158 Hom.: 1647

Bravo AF: 0.148

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.0
Dann	Benign	0.84

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: rs592625; hg19: chr6-32972690;