6-33006064-G-A

Position:

• chr6-33006064-G-A

Variant summary

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

The NM_002119.4(HLA-DOA):​c.*774C>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 0.224 in 152,134 control chromosomes in the GnomAD database, including 3,989 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 0.22 (3989 hom., cov: 32)
  • Exomes 𝑓: 0.038 (0 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.481

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.*774C>T		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	ENST00000229829.7	c.*774C>T		3_prime_UTR_variant	5/5		NM_002119.4	ENSP00000229829	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34028 AN: 151990 Hom.: 3983 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.0385 AC: 1 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.224 AC: 34055 AN: 152108 Hom.: 3989 Cov.: 32 AF XY: 0.222 AC XY: 16509 AN XY: 74338

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.220

Alfa AF: 0.211 Hom.: 1649

Bravo AF: 0.225

Asia WGS AF: 0.254 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.79

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: rs9276977; hg19: chr6-32973841;