rs3128935

Positions:

• chr6-33004627-T-C

Variant summary

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

The NM_002119.4(HLA-DOA):​c.*2211A>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 0.101 in 152,130 control chromosomes in the GnomAD database, including 1,314 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 0.10 (1314 hom., cov: 31)
  • Exomes 𝑓: 0.060 (0 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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 (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DOA	NM_002119.4	c.*2211A>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.*2211A>G		3_prime_UTR_variant	5/5		NM_002119.4	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15338 AN: 151962 Hom.: 1309 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0600 AC: 3 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 3 AN XY: 36

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0500

GnomAD4 genome AF: 0.101 AC: 15366 AN: 152080 Hom.: 1314 Cov.: 31 AF XY: 0.100 AC XY: 7466 AN XY: 74338

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.0110

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0501 Hom.: 556

Bravo AF: 0.115

Asia WGS AF: 0.101 AC: 352 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	1.7
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3128935; hg19: chr6-32972404;