6-32664858-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002123.5(HLA-DQB1):c.319T>C(p.Leu107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,067,978 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (3 hom., cov: 18)
  • Exomes 𝑓: 0.00017 (19 hom.)
• Consequence: HLA-DQB1 NM_002123.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-32664858-A-G is Benign according to our data. Variant chr6-32664858-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656472.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.69 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQB1	NM_002123.5	c.319T>C	p.Leu107=	synonymous_variant	2/5	ENST00000434651.7
HLA-DQB1	NM_001243961.2	c.319T>C	p.Leu107=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.319T>C	p.Leu107=	synonymous_variant	2/5		NM_002123.5	P2

Frequencies

GnomAD3 genomes AF: 0.000272 AC: 32 AN: 117568 Hom.: 3 Cov.: 18

Gnomad AFR AF: 0.0000656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000242

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000382

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000457

Gnomad OTH AF: 0.000658

GnomAD3 exomes AF: 0.000244 AC: 35 AN: 143434 Hom.: 6 AF XY: 0.000252 AC XY: 20 AN XY: 79446

Gnomad AFR exome AF: 0.000118

Gnomad AMR exome AF: 0.000323

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000403

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000174 AC: 165 AN: 950336 Hom.: 19 Cov.: 25 AF XY: 0.000170 AC XY: 82 AN XY: 483526

Gnomad4 AFR exome AF: 0.0000431

Gnomad4 AMR exome AF: 0.000176

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000299

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000230

Gnomad4 NFE exome AF: 0.000217

Gnomad4 OTH exome AF: 0.000191

GnomAD4 genome AF: 0.000272 AC: 32 AN: 117642 Hom.: 3 Cov.: 18 AF XY: 0.000263 AC XY: 15 AN XY: 57014

Gnomad4 AFR AF: 0.0000654

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000243

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000382

Gnomad4 NFE AF: 0.000457

Gnomad4 OTH AF: 0.000650

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

HLA-DQB1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.070
Dann	Benign	0.24

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: rs9274384; hg19: chr6-32632635;