rs1049110

Variant names:

• chr6-32759026-C-A
• rs1049110
• NM_001300790.2:c.470G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32759026-C-A
• chr6-32759026-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001300790.2(HLA-DQB2):​c.470G>T​(p.Arg157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 38)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• Publications: 38 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33186808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.470G>T	p.Arg157Leu	missense_variant	Exon 3 of 6	ENST00000437316.7	NP_001287719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.470G>T	p.Arg157Leu	missense_variant	Exon 3 of 6	6	NM_001300790.2	ENSP00000396330.2
HLA-DQB2	ENST00000435145.6	c.470G>T	p.Arg157Leu	missense_variant	Exon 3 of 5	6		ENSP00000410512.2
HLA-DQB2	ENST00000411527.5	c.470G>T	p.Arg157Leu	missense_variant	Exon 3 of 5	6		ENSP00000390431.1
HLA-DQB2	ENST00000427449.1	c.464G>T	p.Arg155Leu	missense_variant	Exon 3 of 4	6		ENSP00000415997.1

Frequencies

GnomAD3 genomes Cov.: 38

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452002 Hom.: 0 Cov.: 90 AF XY: 0.00000138 AC XY: 1 AN XY: 722366

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33190

American (AMR) AF: 0.00 AC: 0 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

East Asian (EAS) AF: 0.00 AC: 0 AN: 38918

South Asian (SAS) AF: 0.00 AC: 0 AN: 85382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105642

Other (OTH) AF: 0.00 AC: 0 AN: 59984

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	.;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.032	N
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.84
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Benign	0.084
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.85	.;P;.
Vest4		0.43
MutPred		0.65		Loss of disorder (P = 0.1004);Loss of disorder (P = 0.1004);Loss of disorder (P = 0.1004);
MVP		0.28
MPC		1.4
ClinPred		0.93	D
GERP RS		-2.2
gMVP		0.63
Mutation Taster		=94/6	polymorphism

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: rs1049110; hg19: chr6-32726803;