rs2621326

Variant names:

• chr6-32816119-G-A
• rs2621326
• NM_002120.4:c.91+742C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32816119-G-A
• chr6-32816119-G-C
• chr6-32816119-G-T

Variant summary

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

The NM_002120.4(HLA-DOB):​c.91+742C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,908 control chromosomes in the GnomAD database, including 14,643 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 0.44 (14643 hom., cov: 31)
• Consequence: HLA-DOB NM_002120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 30 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.91+742C>T		intron_variant	Intron 1 of 5	ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7	c.91+742C>T		intron_variant	Intron 1 of 5	6	NM_002120.4	ENSP00000390020.2
ENSG00000250264	ENST00000452392.2	c.2024+742C>T		intron_variant	Intron 12 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66204 AN: 151790 Hom.: 14624 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.436 AC: 66259 AN: 151908 Hom.: 14643 Cov.: 31 AF XY: 0.446 AC XY: 33123 AN XY: 74256

African (AFR) AF: 0.396 AC: 16391 AN: 41400

American (AMR) AF: 0.465 AC: 7103 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3472

East Asian (EAS) AF: 0.596 AC: 3075 AN: 5162

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4814

European-Finnish (FIN) AF: 0.548 AC: 5773 AN: 10526

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28183 AN: 67938

Other (OTH) AF: 0.439 AC: 928 AN: 2114

Alfa AF: 0.422 Hom.: 55518

Bravo AF: 0.425

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.43
PhyloP100		-0.063
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: rs2621326; hg19: chr6-32783896;