rs376892

Positions:

• chr6-33005110-G-A
• chr6-33005110-G-C
• chr6-33005110-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.*1728C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,358 control chromosomes in the GnomAD database, including 9,411 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 0.33 (9399 hom., cov: 32)
  • Exomes 𝑓: 0.24 (12 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DOA	NM_002119.4	c.*1728C>T		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.*1728C>T		3_prime_UTR_variant	5/5		NM_002119.4	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50723 AN: 151922 Hom.: 9394 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.239 AC: 76 AN: 318 Hom.: 12 Cov.: 0 AF XY: 0.246 AC XY: 58 AN XY: 236

Gnomad4 AFR exome AF: 0.667

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.334 AC: 50768 AN: 152040 Hom.: 9399 Cov.: 32 AF XY: 0.331 AC XY: 24571 AN XY: 74330

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.346

Alfa AF: 0.279 Hom.: 7554

Bravo AF: 0.342

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.38

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: rs376892; hg19: chr6-32972887;