6-33006624-G-T

Position:

• chr6-33006624-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.*214C>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 0.416 in 673,018 control chromosomes in the GnomAD database, including 60,142 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 0.41 (12761 hom., cov: 31)
  • Exomes 𝑓: 0.42 (47381 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

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]

HLA-DOA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.*214C>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	c.*214C>A		3_prime_UTR_variant	5/5		NM_002119.4	ENSP00000229829.3
HLA-DOA	ENST00000490305.5	n.385C>A		non_coding_transcript_exon_variant	3/3	6

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61600 AN: 151810 Hom.: 12750 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.419 AC: 218519 AN: 521090 Hom.: 47381 Cov.: 6 AF XY: 0.419 AC XY: 116849 AN XY: 278550

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.421

GnomAD4 genome AF: 0.406 AC: 61650 AN: 151928 Hom.: 12761 Cov.: 31 AF XY: 0.407 AC XY: 30213 AN XY: 74272

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.383

Alfa AF: 0.420 Hom.: 22871

Bravo AF: 0.395

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.82

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: rs2581; hg19: chr6-32974401; COSMIC: COSV57714456; COSMIC: COSV57714456;