6-32816843-C-T

Position:

• chr6-32816843-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002120.4(HLA-DOB):​c.91+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,601,474 control chromosomes in the GnomAD database, including 73,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (6382 hom., cov: 32)
  • Exomes 𝑓: 0.30 (66955 hom.)
• Consequence: HLA-DOB NM_002120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 6-32816843-C-T is Benign according to our data. Variant chr6-32816843-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.91+18G>A		intron_variant		ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7	c.91+18G>A		intron_variant		6	NM_002120.4	ENSP00000390020.2
ENSG00000250264	ENST00000452392.2	c.2024+18G>A		intron_variant		2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42096 AN: 151854 Hom.: 6374 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.292

GnomAD3 exomes AF: 0.336 AC: 81586 AN: 242998 Hom.: 14499 AF XY: 0.336 AC XY: 44506 AN XY: 132520

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.441

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.364

Gnomad SAS exome AF: 0.407

Gnomad FIN exome AF: 0.381

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.298 AC: 431376 AN: 1449500 Hom.: 66955 Cov.: 28 AF XY: 0.301 AC XY: 217021 AN XY: 721820

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.277 AC: 42117 AN: 151974 Hom.: 6382 Cov.: 32 AF XY: 0.285 AC XY: 21182 AN XY: 74252

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.292

Alfa AF: 0.286 Hom.: 7464

Bravo AF: 0.270

Asia WGS AF: 0.354 AC: 1231 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.91
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071472; hg19: chr6-32784620; COSMIC: COSV66502339; COSMIC: COSV66502339;