rs1130380

chr6-32664917-C-Achr6-32664917-C-Gchr6-32664917-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_002123.5(HLA-DQB1):c.260G>T(p.Arg87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB1 NM_002123.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003316313).
• BP6: Variant 6-32664917-C-A is Benign according to our data. Variant chr6-32664917-C-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome at 202 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQB1	NM_002123.5	c.260G>T	p.Arg87Leu	missense_variant	2/5	ENST00000434651.7
HLA-DQB1	NM_001243961.2	c.260G>T	p.Arg87Leu	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.260G>T	p.Arg87Leu	missense_variant	2/5		NM_002123.5	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 126488 Hom.: 0 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.0000301

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000972

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000695

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00670 AC: 1046 AN: 156124 Hom.: 202 AF XY: 0.00799 AC XY: 687 AN XY: 86002

Gnomad AFR exome AF: 0.00238

Gnomad AMR exome AF: 0.00201

Gnomad ASJ exome AF: 0.00799

Gnomad EAS exome AF: 0.000648

Gnomad SAS exome AF: 0.0178

Gnomad FIN exome AF: 0.00338

Gnomad NFE exome AF: 0.00708

Gnomad OTH exome AF: 0.00418

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000168 AC: 203 AN: 1205198 Hom.: 0 Cov.: 31 AF XY: 0.000171 AC XY: 104 AN XY: 606966

Gnomad4 AFR exome AF: 0.0000695

Gnomad4 AMR exome AF: 0.0000726

Gnomad4 ASJ exome AF: 0.0000851

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000604

Gnomad4 FIN exome AF: 0.000159

Gnomad4 NFE exome AF: 0.000147

Gnomad4 OTH exome AF: 0.000137

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000632 AC: 8 AN: 126580 Hom.: 0 Cov.: 20 AF XY: 0.000113 AC XY: 7 AN XY: 61712

Gnomad4 AFR AF: 0.0000300

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000972

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000695

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0539 Hom.: 384

ExAC AF: 0.0394 AC: 4674

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	12
Dann	Benign	0.80
DEOGEN2	Benign	0.018	T;T;.;.
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.16	T;T;.;T
MetaRNN	Benign	0.0033	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	D;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.9	D;D;D;D
REVEL	Benign	0.088
Sift	Benign	0.065	T;D;D;D
Sift4G	Uncertain	0.021	D;D;D;D
Polyphen		0.0010	B;.;B;B
Vest4		0.13
MPC		0.69
ClinPred		0.024	T
GERP RS		0.19
gMVP		0.32

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: rs1130380; hg19: chr6-32632694; COSMIC: COSV100891380; COSMIC: COSV100891380;