rs1049225

Variant names:

• chr6-32659970-A-C
• rs1049225
• NM_002123.5:c.*266T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-32659970-A-C
• chr6-32659970-A-G
• chr6-32659970-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002123.5(HLA-DQB1):​c.*266T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000984 in 101,630 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 26)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: HLA-DQB1 NM_002123.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• Publications: 0 publications found

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-AS1 (HGNC:39762): (HLA-DQB1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.*266T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000434651.7	NP_002114.3
HLA-DQB1-AS1	NR_133907.1	n.91A>C		non_coding_transcript_exon_variant	Exon 1 of 2
HLA-DQB1	NM_001243961.2	c.*266T>G		3_prime_UTR_variant	Exon 6 of 6		NP_001230890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.*266T>G		3_prime_UTR_variant	Exon 5 of 5	6	NM_002123.5	ENSP00000407332.2
HLA-DQB1	ENST00000374943.8	c.*266T>G		3_prime_UTR_variant	Exon 6 of 6	6		ENSP00000364080.4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000984 AC: 1 AN: 101630 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 52570

⚠️ 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: 3846

American (AMR) AF: 0.00 AC: 0 AN: 2702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3044

East Asian (EAS) AF: 0.00 AC: 0 AN: 8048

South Asian (SAS) AF: 0.00 AC: 0 AN: 5860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 472

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63278

Other (OTH) AF: 0.000156 AC: 1 AN: 6416

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.79
DANN	Benign	0.43
PhyloP100		0.28

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

Other links and lift over

dbSNP: rs1049225; hg19: chr6-32627747;