chr6-33004865-C-T

Variant names:

• chr6-33004865-C-T
• rs1044429
• NM_002119.4:c.*1973G>A

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.*1973G>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 0.125 in 152,274 control chromosomes in the GnomAD database, including 1,439 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 0.12 (1438 hom., cov: 32)
  • Exomes 𝑓: 0.089 (1 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 33 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOA	NM_002119.4	MANE Select	c.*1973G>A		3_prime_UTR	Exon 5 of 5	NP_002110.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOA	ENST00000229829.7	TSL:6 MANE Select	c.*1973G>A		3_prime_UTR	Exon 5 of 5	ENSP00000229829.3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19008 AN: 152100 Hom.: 1439 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0893 AC: 5 AN: 56 Hom.: 1 Cov.: 0 AF XY: 0.0435 AC XY: 2 AN XY: 46

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0833 AC: 4 AN: 48

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0628932), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.125 AC: 19022 AN: 152218 Hom.: 1438 Cov.: 32 AF XY: 0.130 AC XY: 9651 AN XY: 74414

African (AFR) AF: 0.0571 AC: 2371 AN: 41546

American (AMR) AF: 0.127 AC: 1939 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1255 AN: 5176

South Asian (SAS) AF: 0.268 AC: 1290 AN: 4820

European-Finnish (FIN) AF: 0.117 AC: 1244 AN: 10590

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9407 AN: 67994

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.144 Hom.: 7461

Bravo AF: 0.122

Asia WGS AF: 0.267 AC: 929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		-0.085
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: rs1044429; hg19: chr6-32972642;