rs592625

Variant names:

• chr6-33004913-T-C
• rs592625
• NM_002119.4:c.*1925A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-33004913-T-C
• chr6-33004913-T-G

Variant summary

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

The ENST00000229829.7(HLA-DOA):​c.*1925A>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 0.149 in 152,260 control chromosomes in the GnomAD database, including 1,897 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 0.15 (1896 hom., cov: 32)
  • Exomes 𝑓: 0.29 (1 hom.)
• Consequence: HLA-DOA ENST00000229829.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• Publications: 19 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000229829.7. 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.*1925A>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.*1925A>G		3_prime_UTR	Exon 5 of 5	ENSP00000229829.3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22672 AN: 152126 Hom.: 1894 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.286 AC: 4 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

⚠️ 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) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

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

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

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.149 AC: 22693 AN: 152246 Hom.: 1896 Cov.: 32 AF XY: 0.153 AC XY: 11407 AN XY: 74446

African (AFR) AF: 0.117 AC: 4841 AN: 41548

American (AMR) AF: 0.141 AC: 2160 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5176

South Asian (SAS) AF: 0.293 AC: 1415 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1251 AN: 10602

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9801 AN: 68006

Other (OTH) AF: 0.181 AC: 384 AN: 2116

Alfa AF: 0.152 Hom.: 5240

Bravo AF: 0.148

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.84
PhyloP100		0.78
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: rs592625; hg19: chr6-32972690;