6-32666527-G-GAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002123.5(HLA-DQB1):c.80_81insTT(p.Leu28SerfsTer33) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000871 in 1,158,982 control chromosomes in the GnomAD database, including 98 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. S27S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0012 (4 hom., cov: 28)
  • Exomes 𝑓: 0.00082 (94 hom.)
• Consequence: HLA-DQB1 NM_002123.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.350

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-32666527-G-GAA is Benign according to our data. Variant chr6-32666527-G-GAA is described in ClinVar as [Benign]. Clinvar id is 2656475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQB1	NM_002123.5	c.80_81insTT	p.Leu28SerfsTer33	frameshift_variant	1/5	ENST00000434651.7
HLA-DQB1	NM_001243961.2	c.80_81insTT	p.Leu28SerfsTer33	frameshift_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.80_81insTT	p.Leu28SerfsTer33	frameshift_variant	1/5		NM_002123.5	P2

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 182 AN: 151650 Hom.: 4 Cov.: 28

Gnomad AFR AF: 0.000630

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00110 AC: 194 AN: 176842 Hom.: 14 AF XY: 0.00108 AC XY: 105 AN XY: 97082

Gnomad AFR exome AF: 0.000430

Gnomad AMR exome AF: 0.000218

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0122

Gnomad SAS exome AF: 0.00348

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000335

Gnomad OTH exome AF: 0.000752

GnomAD4 exome AF: 0.000823 AC: 829 AN: 1007214 Hom.: 94 Cov.: 17 AF XY: 0.000931 AC XY: 478 AN XY: 513476

Gnomad4 AFR exome AF: 0.000475

Gnomad4 AMR exome AF: 0.000286

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00752

Gnomad4 SAS exome AF: 0.00430

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000287

Gnomad4 OTH exome AF: 0.00576

GnomAD4 genome AF: 0.00119 AC: 181 AN: 151768 Hom.: 4 Cov.: 28 AF XY: 0.00140 AC XY: 104 AN XY: 74126

Gnomad4 AFR AF: 0.000628

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0167

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00190

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

HLA-DQB1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs778891121; hg19: chr6-32634304;