chr6-33005110-G-A

Variant names:

• chr6-33005110-G-A
• rs376892
• NM_002119.4:c.*1728C>T

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.*1728C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,358 control chromosomes in the GnomAD database, including 9,411 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 0.33 (9399 hom., cov: 32)
  • Exomes 𝑓: 0.24 (12 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOA	NM_002119.4	MANE Select	c.*1728C>T		3_prime_UTR	Exon 5 of 5	NP_002110.1	A0A1V0E3R8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOA	ENST00000229829.7	TSL:6 MANE Select	c.*1728C>T		3_prime_UTR	Exon 5 of 5	ENSP00000229829.3	P06340
	HLA-DOA	ENST00000892664.1		c.*1728C>T		3_prime_UTR	Exon 4 of 4	ENSP00000562723.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50723 AN: 151922 Hom.: 9394 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.239 AC: 76 AN: 318 Hom.: 12 Cov.: 0 AF XY: 0.246 AC XY: 58 AN XY: 236

African (AFR) AF: 0.667 AC: 8 AN: 12

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

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

European-Non Finnish (NFE) AF: 0.232 AC: 64 AN: 276

Other (OTH) AF: 0.167 AC: 2 AN: 12

GnomAD4 genome AF: 0.334 AC: 50768 AN: 152040 Hom.: 9399 Cov.: 32 AF XY: 0.331 AC XY: 24571 AN XY: 74330

African (AFR) AF: 0.485 AC: 20114 AN: 41454

American (AMR) AF: 0.278 AC: 4253 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1236 AN: 5162

South Asian (SAS) AF: 0.337 AC: 1623 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2364 AN: 10578

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18608 AN: 67946

Other (OTH) AF: 0.346 AC: 731 AN: 2112

Alfa AF: 0.288 Hom.: 20003

Bravo AF: 0.342

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.38
PhyloP100		-0.24
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: rs376892; hg19: chr6-32972887;