NM_002123.5:c.122T>C

Variant names:

• chr6-32665055-A-G
• rs9274407
• NM_002123.5:c.122T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002123.5(HLA-DQB1):​c.122T>C​(p.Phe41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.0 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB1 NM_002123.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.44
• Publications: 72 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08736211).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB1	NM_002123.5	MANE Select	c.122T>C	p.Phe41Ser	missense	Exon 2 of 5	NP_002114.3
	HLA-DQB1	NM_001243961.2		c.122T>C	p.Phe41Ser	missense	Exon 2 of 6	NP_001230890.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB1	ENST00000434651.7	TSL:6 MANE Select	c.122T>C	p.Phe41Ser	missense	Exon 2 of 5	ENSP00000407332.2
	HLA-DQB1	ENST00000374943.8	TSL:6	c.122T>C	p.Phe41Ser	missense	Exon 2 of 6	ENSP00000364080.4
	HLA-DQB1	ENST00000399084.5	TSL:6	c.122T>C	p.Phe41Ser	missense	Exon 3 of 6	ENSP00000382034.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 130260 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: 1222162 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 612118

African (AFR) AF: 0.00 AC: 0 AN: 27068

American (AMR) AF: 0.00 AC: 0 AN: 39622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23026

East Asian (EAS) AF: 0.00 AC: 0 AN: 36414

South Asian (SAS) AF: 0.00 AC: 0 AN: 74884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4524

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 916246

Other (OTH) AF: 0.00 AC: 0 AN: 50718

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 130260 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 63264

African (AFR) AF: 0.00 AC: 0 AN: 34006

American (AMR) AF: 0.00 AC: 0 AN: 13492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3180

East Asian (EAS) AF: 0.00 AC: 0 AN: 4644

South Asian (SAS) AF: 0.00 AC: 0 AN: 3692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59396

Other (OTH) AF: 0.00 AC: 0 AN: 1708

Alfa AF: 0.00 Hom.: 1454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.0010
DANN	Benign	0.90
DEOGEN2	Benign	0.035	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.83	T
PhyloP100		-7.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.097
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.21	T
Polyphen		0.37	B
Vest4		0.21
MutPred		0.28		Gain of disorder (P = 0.0078)
MVP		0.055
MPC		1.0
ClinPred		0.56	D
GERP RS		-8.3
gMVP		0.60
Mutation Taster		=97/3	polymorphism

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: rs9274407; hg19: chr6-32632832;