6-32816843-C-T

Variant names:

• chr6-32816843-C-T
• rs2071472
• NM_002120.4:c.91+18G>A

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+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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 41 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=-0.98).
• 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 rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.91+18G>A		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+18G>A		intron_variant	Intron 1 of 5	6	NM_002120.4	ENSP00000390020.2
ENSG00000250264	ENST00000452392.2	c.2024+18G>A		intron_variant	Intron 12 of 14	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

GnomAD2 exomes AF: 0.336 AC: 81586 AN: 242998 AF XY: 0.336

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 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

African (AFR) AF: 0.163 AC: 5387 AN: 33048

American (AMR) AF: 0.427 AC: 18901 AN: 44272

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 8840 AN: 25956

East Asian (EAS) AF: 0.351 AC: 13880 AN: 39570

South Asian (SAS) AF: 0.403 AC: 34500 AN: 85606

European-Finnish (FIN) AF: 0.373 AC: 19499 AN: 52240

Middle Eastern (MID) AF: 0.292 AC: 1673 AN: 5736

European-Non Finnish (NFE) AF: 0.282 AC: 311210 AN: 1103152

Other (OTH) AF: 0.292 AC: 17486 AN: 59920

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

African (AFR) AF: 0.157 AC: 6512 AN: 41448

American (AMR) AF: 0.360 AC: 5500 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3468

East Asian (EAS) AF: 0.358 AC: 1852 AN: 5176

South Asian (SAS) AF: 0.401 AC: 1928 AN: 4806

European-Finnish (FIN) AF: 0.377 AC: 3967 AN: 10528

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20053 AN: 67944

Other (OTH) AF: 0.292 AC: 617 AN: 2112

Alfa AF: 0.280 Hom.: 19243

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
PhyloP100		-2.6
PromoterAI		-0.0057	Neutral
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: rs2071472; hg19: chr6-32784620; COSMIC: COSV66502339; COSMIC: COSV66502339;