Variant chr6-32662082-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.995

Variant links:

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]

HLA-DQB1 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.546T>C	p.Asn182=	synonymous_variant	3/5	ENST00000434651.7	NP_002114.3
HLA-DQB1	NM_001243961.2 linkuse as main transcript	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 linkuse as main transcript	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.505

AC XY:

305773

AN XY:

604990

show subpopulations

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.:

AF XY:

0.501

AC XY:

29021

AN XY:

57920

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over