6-33005822-C-T

Position:

• chr6-33005822-C-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.*1016G>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 0.133 in 152,170 control chromosomes in the GnomAD database, including 1,477 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 0.13 (1476 hom., cov: 31)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DOA	NM_002119.4	c.*1016G>A		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.*1016G>A		3_prime_UTR_variant	5/5		NM_002119.4	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20283 AN: 151924 Hom.: 1472 Cov.: 31

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.109 AC: 14 AN: 128 Hom.: 1 Cov.: 0 AF XY: 0.0745 AC XY: 7 AN XY: 94

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.133 AC: 20290 AN: 152042 Hom.: 1476 Cov.: 31 AF XY: 0.135 AC XY: 9997 AN XY: 74306

Gnomad4 AFR AF: 0.0833

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.126

Alfa AF: 0.138 Hom.: 1094

Bravo AF: 0.127

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.15

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: rs9276975; hg19: chr6-32973599;