rs6908943

Positions:

• chr6-32667519-C-T

Variant summary

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

The ENST00000399084.5(HLA-DQB1):​c.-64+749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 123,710 control chromosomes in the GnomAD database, including 3,162 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 (3162 hom., cov: 27)
• Consequence: HLA-DQB1 ENST00000399084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000399084.5	c.-64+749G>A		intron_variant				ENSP00000382034	P2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 27404 AN: 123610 Hom.: 3160 Cov.: 27

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.0986

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.222 AC: 27417 AN: 123710 Hom.: 3162 Cov.: 27 AF XY: 0.218 AC XY: 13173 AN XY: 60330

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.0986

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.243

Alfa AF: 0.201 Hom.: 475

Bravo AF: 0.200

Asia WGS AF: 0.218 AC: 754 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
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: rs6908943; hg19: chr6-32635296;