rs7383287

Variant names:

• chr6-32815309-A-G
• rs7383287
• NM_002120.4:c.96T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002120.4(HLA-DOB):​c.96T>C​(p.Asp32Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,613,526 control chromosomes in the GnomAD database, including 33,469 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 0.19 (2772 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30697 hom.)
• Consequence: HLA-DOB NM_002120.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 47 publications found

Genes affected

HLA-DOB (HGNC:4937): (major histocompatibility complex, class II, DO beta) HLA-DOB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DOA) and a beta chain (DOB), both anchored in the membrane. It is located in intracellular vesicles. DO suppresses peptide loading of MHC class II molecules by inhibiting HLA-DM. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.076).
• BP7: Synonymous conserved (PhyloP=0.046 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.96T>C	p.Asp32Asp	synonymous_variant	Exon 2 of 6	ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7	c.96T>C	p.Asp32Asp	synonymous_variant	Exon 2 of 6	6	NM_002120.4	ENSP00000390020.2
ENSG00000250264	ENST00000452392.2	c.2025-108T>C		intron_variant	Intron 12 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28196 AN: 152034 Hom.: 2773 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.176 AC: 44098 AN: 251012 AF XY: 0.181

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.0449

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.200 AC: 292584 AN: 1461374 Hom.: 30697 Cov.: 38 AF XY: 0.201 AC XY: 146455 AN XY: 726902

African (AFR) AF: 0.171 AC: 5728 AN: 33470

American (AMR) AF: 0.125 AC: 5594 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5856 AN: 26136

East Asian (EAS) AF: 0.0433 AC: 1719 AN: 39694

South Asian (SAS) AF: 0.164 AC: 14142 AN: 86254

European-Finnish (FIN) AF: 0.171 AC: 9157 AN: 53406

Middle Eastern (MID) AF: 0.215 AC: 1237 AN: 5766

European-Non Finnish (NFE) AF: 0.214 AC: 237559 AN: 1111544

Other (OTH) AF: 0.192 AC: 11592 AN: 60382

GnomAD4 genome AF: 0.185 AC: 28193 AN: 152152 Hom.: 2772 Cov.: 32 AF XY: 0.180 AC XY: 13394 AN XY: 74390

African (AFR) AF: 0.175 AC: 7269 AN: 41504

American (AMR) AF: 0.145 AC: 2216 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 751 AN: 3466

East Asian (EAS) AF: 0.0404 AC: 209 AN: 5178

South Asian (SAS) AF: 0.145 AC: 699 AN: 4830

European-Finnish (FIN) AF: 0.173 AC: 1825 AN: 10574

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14598 AN: 67986

Other (OTH) AF: 0.180 AC: 381 AN: 2112

Alfa AF: 0.204 Hom.: 13761

Bravo AF: 0.181

Asia WGS AF: 0.100 AC: 348 AN: 3478

EpiCase AF: 0.232

EpiControl AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.1
DANN	Benign	0.86
PhyloP100		0.046
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: rs7383287; hg19: chr6-32783086; COSMIC: COSV71270982;