6-32817006-C-T

Variant names:

• chr6-32817006-C-T
• rs2071469
• ENST00000452392.2:c.1933-54G>A

Variant summary

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

The ENST00000452392.2(ENSG00000250264):​c.1933-54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,333,512 control chromosomes in the GnomAD database, including 96,503 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 0.35 (10254 hom., cov: 32)
  • Exomes 𝑓: 0.37 (86249 hom.)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771
• Publications: 49 publications found

Genes affected

ENSG00000250264 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000452392.2. 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-DOB	NM_002120.4	MANE Select	c.-55G>A		upstream_gene	N/A	NP_002111.1	P13765

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1933-54G>A		intron	N/A	ENSP00000391806.2	E7ENX8
	HLA-DOB	ENST00000900286.1		c.-55G>A		5_prime_UTR	Exon 1 of 6	ENSP00000570345.1
	HLA-DOB	ENST00000944925.1		c.-55G>A		5_prime_UTR	Exon 1 of 4	ENSP00000614984.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53813 AN: 151840 Hom.: 10247 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.374 AC: 442311 AN: 1181554 Hom.: 86249 Cov.: 15 AF XY: 0.376 AC XY: 225897 AN XY: 600544

African (AFR) AF: 0.229 AC: 6338 AN: 27664

American (AMR) AF: 0.471 AC: 20161 AN: 42808

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 9067 AN: 24028

East Asian (EAS) AF: 0.491 AC: 18828 AN: 38332

South Asian (SAS) AF: 0.443 AC: 35344 AN: 79776

European-Finnish (FIN) AF: 0.492 AC: 25436 AN: 51718

Middle Eastern (MID) AF: 0.350 AC: 1808 AN: 5172

European-Non Finnish (NFE) AF: 0.356 AC: 306807 AN: 861084

Other (OTH) AF: 0.363 AC: 18522 AN: 50972

GnomAD4 genome AF: 0.354 AC: 53842 AN: 151958 Hom.: 10254 Cov.: 32 AF XY: 0.364 AC XY: 27010 AN XY: 74258

African (AFR) AF: 0.224 AC: 9279 AN: 41434

American (AMR) AF: 0.407 AC: 6222 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1267 AN: 3468

East Asian (EAS) AF: 0.534 AC: 2758 AN: 5164

South Asian (SAS) AF: 0.455 AC: 2189 AN: 4806

European-Finnish (FIN) AF: 0.499 AC: 5254 AN: 10536

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25464 AN: 67966

Other (OTH) AF: 0.358 AC: 754 AN: 2108

Alfa AF: 0.364 Hom.: 26346

Bravo AF: 0.340

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		-0.77
PromoterAI		-0.15	Neutral
Mutation Taster		=300/0	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

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

Other links and lift over

dbSNP: rs2071469;

hg19: chr6-32784783;

COSMIC: COSV66503396;

COSMIC: COSV66503396;