rs3128935

Variant names:

• chr6-33004627-T-C
• rs3128935
• NM_002119.4:c.*2211A>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.*2211A>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 0.101 in 152,130 control chromosomes in the GnomAD database, including 1,314 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 0.10 (1314 hom., cov: 31)
  • Exomes 𝑓: 0.060 (0 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 24 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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.*2211A>G		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.*2211A>G		3_prime_UTR	Exon 5 of 5	ENSP00000229829.3
	HLA-DOA	ENST00000892664.1		c.*2211A>G		3_prime_UTR	Exon 4 of 4	ENSP00000562723.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15338 AN: 151962 Hom.: 1309 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0600 AC: 3 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 3 AN XY: 36

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

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0500 AC: 2 AN: 40

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.101 AC: 15366 AN: 152080 Hom.: 1314 Cov.: 31 AF XY: 0.100 AC XY: 7466 AN XY: 74338

African (AFR) AF: 0.230 AC: 9512 AN: 41424

American (AMR) AF: 0.104 AC: 1590 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3470

East Asian (EAS) AF: 0.157 AC: 812 AN: 5170

South Asian (SAS) AF: 0.0895 AC: 431 AN: 4816

European-Finnish (FIN) AF: 0.0110 AC: 117 AN: 10606

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0349 AC: 2376 AN: 68000

Other (OTH) AF: 0.109 AC: 229 AN: 2108

Alfa AF: 0.0576 Hom.: 2000

Bravo AF: 0.115

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.44
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3128935; hg19: chr6-32972404;