rs9274477

chr6-32665936-A-Gchr6-32665936-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002123.5(HLA-DQB1):c.109+563T>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: 𝑓 0.27 (5522 hom., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB1 NM_002123.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High Homozygotes in GnomAd at 5523 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQB1	NM_002123.5	c.109+563T>C		intron_variant		ENST00000434651.7
HLA-DQB1	NM_001243961.2	c.109+563T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.109+563T>C		intron_variant			NM_002123.5	P2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 32447 AN: 119700 Hom.: 5523 Cov.: 19

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.287

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.271 AC: 32455 AN: 119806 Hom.: 5522 Cov.: 19 AF XY: 0.256 AC XY: 14825 AN XY: 57958

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.284

Alfa AF: 0.378 Hom.: 1087

Asia WGS AF: 0.316 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.0
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9274477; hg19: chr6-32633713;