6-32668069-C-G

Position:

• chr6-32668069-C-G

Variant summary

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

The ENST00000399084.5(HLA-DQB1):​c.-64+199G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 151,674 control chromosomes in the GnomAD database, including 44,326 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 0.76 (44326 hom., cov: 30)
• Consequence: HLA-DQB1 ENST00000399084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQB1	ENST00000399084.5	c.-64+199G>C		intron_variant				P2

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115555 AN: 151556 Hom.: 44298 Cov.: 30

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.882

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.797

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.762 AC: 115640 AN: 151674 Hom.: 44326 Cov.: 30 AF XY: 0.764 AC XY: 56611 AN XY: 74100

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.800

Alfa AF: 0.586 Hom.: 696

Bravo AF: 0.767

Asia WGS AF: 0.886 AC: 3083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9274614; hg19: chr6-32635846;