ENST00000399084.5:c.-63-116G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000399084.5(HLA-DQB1):​c.-63-116G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: not found (cov: 8)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB1 ENST00000399084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 8 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.-179G>C		upstream_gene_variant		ENST00000434651.7	NP_002114.3
HLA-DQB1	NM_001243961.2	c.-179G>C		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>C		upstream_gene_variant		6	NM_002123.5	ENSP00000407332.2
HLA-DQB1	ENST00000374943.8	c.-179G>C		upstream_gene_variant		6		ENSP00000364080.4

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 144742 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76478

African (AFR) AF: 0.00 AC: 0 AN: 3820

American (AMR) AF: 0.00 AC: 0 AN: 3144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3598

East Asian (EAS) AF: 0.00 AC: 0 AN: 8802

South Asian (SAS) AF: 0.00 AC: 0 AN: 12196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 90258

Other (OTH) AF: 0.00 AC: 0 AN: 8488

GnomAD4 genome Cov.: 8

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		-2.1
PromoterAI		-0.21	Neutral

Splicing

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

Other links and lift over

dbSNP: rs78202368; hg19: chr6-32634563;