6-33005504-T-C

Variant names:

• chr6-33005504-T-C
• rs416622
• NM_002119.4:c.*1334A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002119.4(HLA-DOA):​c.*1334A>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 0.475 in 151,628 control chromosomes in the GnomAD database, including 17,559 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 0.47 (17485 hom., cov: 29)
  • Exomes 𝑓: 0.65 (74 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.*1334A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000229829.7	NP_002110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOA	ENST00000229829.7	c.*1334A>G		3_prime_UTR_variant	Exon 5 of 5	6	NM_002119.4	ENSP00000229829.3

Frequencies

GnomAD3 genomes AF: 0.475 AC: 71720 AN: 151148 Hom.: 17469 Cov.: 29

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.649 AC: 235 AN: 362 Hom.: 74 Cov.: 0 AF XY: 0.663 AC XY: 183 AN XY: 276

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.857 AC: 12 AN: 14

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 0.583 AC: 7 AN: 12

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.657 AC: 201 AN: 306

Other (OTH) AF: 0.750 AC: 9 AN: 12

GnomAD4 genome AF: 0.475 AC: 71777 AN: 151266 Hom.: 17485 Cov.: 29 AF XY: 0.476 AC XY: 35170 AN XY: 73866

African (AFR) AF: 0.399 AC: 16441 AN: 41244

American (AMR) AF: 0.400 AC: 6093 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1698 AN: 3456

East Asian (EAS) AF: 0.622 AC: 3168 AN: 5096

South Asian (SAS) AF: 0.564 AC: 2702 AN: 4788

European-Finnish (FIN) AF: 0.489 AC: 5104 AN: 10448

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.517 AC: 35017 AN: 67690

Other (OTH) AF: 0.465 AC: 984 AN: 2114

Alfa AF: 0.494 Hom.: 29310

Bravo AF: 0.462

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.28
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs416622; hg19: chr6-32973281;