rs778891121

Variant names:

• chr6-32666527-G-GAA
• rs778891121
• NM_002123.5:c.80_81insTT

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 2656475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002123.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB1	NM_002123.5	MANE Select	c.80_81insTT	p.Leu28SerfsTer33	frameshift	Exon 1 of 5	NP_002114.3
	HLA-DQB1	NM_001243961.2		c.80_81insTT	p.Leu28SerfsTer33	frameshift	Exon 1 of 6	NP_001230890.1	Q5SU54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB1	ENST00000434651.7	TSL:6 MANE Select	c.80_81insTT	p.Leu28SerfsTer33	frameshift	Exon 1 of 5	ENSP00000407332.2
	HLA-DQB1	ENST00000374943.8	TSL:6	c.80_81insTT	p.Leu28SerfsTer33	frameshift	Exon 1 of 6	ENSP00000364080.4	Q5SU54
	HLA-DQB1	ENST00000399084.5	TSL:6	c.80_81insTT	p.Leu28SerfsTer33	frameshift	Exon 2 of 6	ENSP00000382034.1

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

GnomAD2 exomes AF: 0.00110 AC: 194 AN: 176842 AF XY: 0.00108

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 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

African (AFR) AF: 0.000475 AC: 12 AN: 25268

American (AMR) AF: 0.000286 AC: 9 AN: 31494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20308

East Asian (EAS) AF: 0.00752 AC: 239 AN: 31778

South Asian (SAS) AF: 0.00430 AC: 294 AN: 68412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4322

European-Non Finnish (NFE) AF: 0.0000287 AC: 21 AN: 731090

Other (OTH) AF: 0.00576 AC: 254 AN: 44082

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

African (AFR) AF: 0.000628 AC: 26 AN: 41406

American (AMR) AF: 0.000328 AC: 5 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.0167 AC: 85 AN: 5100

South Asian (SAS) AF: 0.0124 AC: 59 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67922

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.35
Mutation Taster		=194/6	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs778891121; hg19: chr6-32634304;