6-33006774-G-T

Position:

• chr6-33006774-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.*64C>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 0.128 in 1,611,676 control chromosomes in the GnomAD database, including 15,983 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 0.11 (1166 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14817 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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 = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.*64C>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	ENST00000229829.7	c.*64C>A		3_prime_UTR_variant	5/5		NM_002119.4	ENSP00000229829	P1
HLA-DOA	ENST00000490305.5	n.235C>A		non_coding_transcript_exon_variant	3/3
HLA-DOA	ENST00000485901.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16226 AN: 152106 Hom.: 1164 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.144 AC: 35485 AN: 246622 Hom.: 3178 AF XY: 0.152 AC XY: 20372 AN XY: 134406

Gnomad AFR exome AF: 0.0227

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.196

Gnomad SAS exome AF: 0.251

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.130 AC: 189993 AN: 1459452 Hom.: 14817 Cov.: 31 AF XY: 0.135 AC XY: 98135 AN XY: 726154

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.107 AC: 16226 AN: 152224 Hom.: 1166 Cov.: 32 AF XY: 0.111 AC XY: 8226 AN XY: 74408

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.132

Alfa AF: 0.142 Hom.: 2574

Bravo AF: 0.101

Asia WGS AF: 0.246 AC: 855 AN: 3478

EpiCase AF: 0.145

EpiControl AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.57

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: rs2582; hg19: chr6-32974551; COSMIC: COSV57713597; COSMIC: COSV57713597;