rs2647025

chr6-32668172-G-A

Variant summary

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

The ENST00000399084.5(HLA-DQB1):c.-64+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,668 control chromosomes in the GnomAD database, including 6,086 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 (6027 hom., cov: 31)
  • Exomes 𝑓: 0.35 (59 hom.)
• Consequence: HLA-DQB1 ENST00000399084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 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+96C>T		intron_variant				P2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41776 AN: 151726 Hom.: 6020 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.346 AC: 285 AN: 824 Hom.: 59 AF XY: 0.328 AC XY: 135 AN XY: 412

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.192

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.275 AC: 41812 AN: 151844 Hom.: 6027 Cov.: 31 AF XY: 0.279 AC XY: 20733 AN XY: 74200

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.277

Alfa AF: 0.273 Hom.: 6080

Bravo AF: 0.287

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.5
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2647025; hg19: chr6-32635949; COSMIC: COSV66571517; COSMIC: COSV66571517;