6-32666786-C-T

Variant names:

• chr6-32666786-C-T
• rs78202368
• ENST00000399084.5:c.-63-116G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399084.5(HLA-DQB1):​c.-63-116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 211,278 control chromosomes in the GnomAD database, including 1,033 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 0.22 (958 hom., cov: 8)
  • Exomes 𝑓: 0.023 (75 hom.)
• Consequence: HLA-DQB1 ENST00000399084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

Genes affected

HLA-DQB1 (HGNC:4944): (major histocompatibility complex, class II, DQ beta 1) HLA-DQB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and it contains six exons. Exon 1 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. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.-179G>A		upstream_gene_variant		ENST00000434651.7	NP_002114.3
HLA-DQB1	NM_001243961.2	c.-179G>A		upstream_gene_variant			NP_001230890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.-179G>A		upstream_gene_variant		6	NM_002123.5	ENSP00000407332.2
HLA-DQB1	ENST00000374943.8	c.-179G>A		upstream_gene_variant		6		ENSP00000364080.4

Frequencies

GnomAD3 genomes AF: 0.216 AC: 15164 AN: 70280 Hom.: 958 Cov.: 8

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.0234 AC: 3294 AN: 140942 Hom.: 75 AF XY: 0.0241 AC XY: 1796 AN XY: 74446

Gnomad4 AFR exome AF: 0.0205

Gnomad4 AMR exome AF: 0.00996

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.00159

Gnomad4 SAS exome AF: 0.0364

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.0262

Gnomad4 OTH exome AF: 0.0260

GnomAD4 genome AF: 0.216 AC: 15169 AN: 70336 Hom.: 958 Cov.: 8 AF XY: 0.207 AC XY: 7117 AN XY: 34406

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0983

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78202368; hg19: chr6-32634563;