rs7453920

Variant names:

• chr6-32762235-A-G
• rs7453920
• NM_001300790.2:c.98-309T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32762235-A-G
• chr6-32762235-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300790.2(HLA-DQB2):​c.98-309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,988 control chromosomes in the GnomAD database, including 31,980 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31980 hom., cov: 32)
• Consequence: HLA-DQB2 NM_001300790.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 128 publications found

Genes affected

HLA-DQB2 (HGNC:4945): (major histocompatibility complex, class II, DQ beta 2) HLA-DQB2 belongs to the family of HLA class II beta chain paralogs. Class II molecules are heterodimers consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. They play 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). Polymorphisms in the alpha and beta chains specify the peptide binding specificity, and typing for these polymorphisms is routinely done for bone marrow transplantation. However this gene, HLA-DQB2, is not routinely typed, as it is not thought to have an effect on transplantation. There is conflicting evidence in the literature and public sequence databases for the protein-coding capacity of HLA-DQB2. Because there is evidence of transcription and an intact ORF, HLA-DQB2 is represented in Entrez Gene and in RefSeq as a protein-coding locus. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.98-309T>C		intron_variant	Intron 1 of 5	ENST00000437316.7	NP_001287719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.98-309T>C		intron_variant	Intron 1 of 5	6	NM_001300790.2	ENSP00000396330.2
HLA-DQB2	ENST00000435145.6	c.98-309T>C		intron_variant	Intron 1 of 4	6		ENSP00000410512.2
HLA-DQB2	ENST00000411527.5	c.98-309T>C		intron_variant	Intron 1 of 4	6		ENSP00000390431.1
HLA-DQB2	ENST00000427449.1	c.92-309T>C		intron_variant	Intron 1 of 3	6		ENSP00000415997.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97523 AN: 151870 Hom.: 31937 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.695

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.642 AC: 97627 AN: 151988 Hom.: 31980 Cov.: 32 AF XY: 0.650 AC XY: 48253 AN XY: 74276

African (AFR) AF: 0.699 AC: 28974 AN: 41462

American (AMR) AF: 0.697 AC: 10648 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2326 AN: 3466

East Asian (EAS) AF: 0.874 AC: 4520 AN: 5170

South Asian (SAS) AF: 0.815 AC: 3922 AN: 4814

European-Finnish (FIN) AF: 0.583 AC: 6140 AN: 10538

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38745 AN: 67942

Other (OTH) AF: 0.700 AC: 1481 AN: 2116

Alfa AF: 0.594 Hom.: 119173

Bravo AF: 0.654

Asia WGS AF: 0.821 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.15
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7453920; hg19: chr6-32730012;