rs1049130

Positions:

• chr6-32662082-A-G
• chr6-32662082-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_002123.5(HLA-DQB1):​c.546T>C​(p.Asn182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,325,790 control chromosomes in the GnomAD database, including 209,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.50 (17754 hom., cov: 20)
  • Exomes 𝑓: 0.50 (191714 hom.)
• Consequence: HLA-DQB1 NM_002123.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-32662082-A-G is Benign according to our data. Variant chr6-32662082-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.995 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.546T>C	p.Asn182=	synonymous_variant	3/5	ENST00000434651.7	NP_002114.3
HLA-DQB1	NM_001243961.2	c.546T>C	p.Asn182=	synonymous_variant	3/6		NP_001230890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.546T>C	p.Asn182=	synonymous_variant	3/5		NM_002123.5	ENSP00000407332	P2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 59810 AN: 120348 Hom.: 17732 Cov.: 20

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.522

GnomAD3 exomes AF: 0.617 AC: 148641 AN: 240820 Hom.: 48612 AF XY: 0.612 AC XY: 80108 AN XY: 130858

Gnomad AFR exome AF: 0.495

Gnomad AMR exome AF: 0.770

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.815

Gnomad SAS exome AF: 0.643

Gnomad FIN exome AF: 0.616

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.500 AC: 602651 AN: 1205366 Hom.: 191714 Cov.: 37 AF XY: 0.505 AC XY: 305773 AN XY: 604990

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.697

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.798

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.523

GnomAD4 genome AF: 0.497 AC: 59858 AN: 120424 Hom.: 17754 Cov.: 20 AF XY: 0.501 AC XY: 29021 AN XY: 57920

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.529

Alfa AF: 0.545 Hom.: 7311

Asia WGS AF: 0.775 AC: 2699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.081
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1049130; hg19: chr6-32629859; COSMIC: COSV66573493; COSMIC: COSV66573493;