rs1140343

Variant names:

• chr6-32661360-T-C
• rs1140343
• NM_002123.5:c.759A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-32661360-T-C
• chr6-32661360-T-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_002123.5(HLA-DQB1):​c.759A>G​(p.Gln253Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB1 NM_002123.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 25 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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.25 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002123.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB1	NM_002123.5	MANE Select	c.759A>G	p.Gln253Gln	synonymous	Exon 4 of 5	NP_002114.3
	HLA-DQB1	NM_001243961.2		c.759A>G	p.Gln253Gln	synonymous	Exon 4 of 6	NP_001230890.1	Q5SU54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB1	ENST00000434651.7	TSL:6 MANE Select	c.759A>G	p.Gln253Gln	synonymous	Exon 4 of 5	ENSP00000407332.2
	HLA-DQB1	ENST00000374943.8	TSL:6	c.759A>G	p.Gln253Gln	synonymous	Exon 4 of 6	ENSP00000364080.4	Q5SU54
	HLA-DQB1	ENST00000399084.5	TSL:6	c.759A>G	p.Gln253Gln	synonymous	Exon 5 of 6	ENSP00000382034.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 134022 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1163056 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 584672

African (AFR) AF: 0.00 AC: 0 AN: 28750

American (AMR) AF: 0.00 AC: 0 AN: 35048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21448

East Asian (EAS) AF: 0.00 AC: 0 AN: 30234

South Asian (SAS) AF: 0.00 AC: 0 AN: 77242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3540

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 871292

Other (OTH) AF: 0.00 AC: 0 AN: 49594

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 134022 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 64582

African (AFR) AF: 0.00 AC: 0 AN: 37382

American (AMR) AF: 0.00 AC: 0 AN: 11994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3018

East Asian (EAS) AF: 0.00 AC: 0 AN: 4088

South Asian (SAS) AF: 0.00 AC: 0 AN: 4052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62038

Other (OTH) AF: 0.00 AC: 0 AN: 1830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.88
DANN	Benign	0.78
PhyloP100		-0.25

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: rs1140343; hg19: chr6-32629137;