rs3128931

Variant names:

• chr6-33003931-G-A
• rs3128931
• ENST00000892664.1:c.*2907C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33003931-G-A
• chr6-33003931-G-C

Variant summary

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

The ENST00000892664.1(HLA-DOA):​c.*2907C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,852 control chromosomes in the GnomAD database, including 8,821 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 0.31 (8821 hom., cov: 31)
• Consequence: HLA-DOA ENST00000892664.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 21 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000892664.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOA	ENST00000892664.1		c.*2907C>T		downstream_gene	N/A	ENSP00000562723.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47713 AN: 151734 Hom.: 8811 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.314 AC: 47757 AN: 151852 Hom.: 8821 Cov.: 31 AF XY: 0.309 AC XY: 22969 AN XY: 74222

African (AFR) AF: 0.514 AC: 21242 AN: 41360

American (AMR) AF: 0.258 AC: 3948 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3470

East Asian (EAS) AF: 0.342 AC: 1762 AN: 5158

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4812

European-Finnish (FIN) AF: 0.197 AC: 2073 AN: 10536

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15606 AN: 67930

Other (OTH) AF: 0.305 AC: 642 AN: 2104

Alfa AF: 0.262 Hom.: 17733

Bravo AF: 0.328

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		-0.0010

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3128931;

hg19: chr6-32971708;