chr6-32665055-A-T

Variant names:

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

Variant summary

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

The NM_002123.5(HLA-DQB1):​c.122T>A​(p.Phe41Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,307,038 control chromosomes in the GnomAD database, including 424,334 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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: 𝑓 0.76 (39960 hom., cov: 20)
  • Exomes 𝑓: 0.76 (384374 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.067431E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

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>A	p.Phe41Tyr	missense	Exon 2 of 5	NP_002114.3
	HLA-DQB1	NM_001243961.2		c.122T>A	p.Phe41Tyr	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>A	p.Phe41Tyr	missense	Exon 2 of 5	ENSP00000407332.2
	HLA-DQB1	ENST00000374943.8	TSL:6	c.122T>A	p.Phe41Tyr	missense	Exon 2 of 6	ENSP00000364080.4
	HLA-DQB1	ENST00000399084.5	TSL:6	c.122T>A	p.Phe41Tyr	missense	Exon 3 of 6	ENSP00000382034.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 97383 AN: 128718 Hom.: 39939 Cov.: 20

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.814

GnomAD2 exomes AF: 0.774 AC: 136420 AN: 176342 AF XY: 0.785

Gnomad AFR exome AF: 0.606

Gnomad AMR exome AF: 0.751

Gnomad ASJ exome AF: 0.914

Gnomad EAS exome AF: 0.730

Gnomad FIN exome AF: 0.713

Gnomad NFE exome AF: 0.795

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.757 AC: 892271 AN: 1178198 Hom.: 384374 Cov.: 28 AF XY: 0.760 AC XY: 449379 AN XY: 591258

African (AFR) AF: 0.621 AC: 15614 AN: 25152

American (AMR) AF: 0.763 AC: 29620 AN: 38838

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 20408 AN: 22790

East Asian (EAS) AF: 0.636 AC: 22647 AN: 35604

South Asian (SAS) AF: 0.760 AC: 56176 AN: 73872

European-Finnish (FIN) AF: 0.734 AC: 35469 AN: 48308

Middle Eastern (MID) AF: 0.840 AC: 3746 AN: 4458

European-Non Finnish (NFE) AF: 0.763 AC: 671210 AN: 880120

Other (OTH) AF: 0.762 AC: 37381 AN: 49056

GnomAD4 genome AF: 0.756 AC: 97457 AN: 128840 Hom.: 39960 Cov.: 20 AF XY: 0.752 AC XY: 47115 AN XY: 62656

African (AFR) AF: 0.673 AC: 22604 AN: 33574

American (AMR) AF: 0.788 AC: 10569 AN: 13410

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 2876 AN: 3160

East Asian (EAS) AF: 0.722 AC: 3309 AN: 4584

South Asian (SAS) AF: 0.756 AC: 2753 AN: 3642

European-Finnish (FIN) AF: 0.734 AC: 6587 AN: 8970

Middle Eastern (MID) AF: 0.851 AC: 206 AN: 242

European-Non Finnish (NFE) AF: 0.791 AC: 46463 AN: 58716

Other (OTH) AF: 0.812 AC: 1391 AN: 1714

Alfa AF: 0.644 Hom.: 1454

ESP6500AA AF: 0.719 AC: 3001

ESP6500EA AF: 0.813 AC: 6802

ExAC AF: 0.779 AC: 93224

Asia WGS AF: 0.792 AC: 2757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0010
DANN	Benign	0.69
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.0091	T
MetaRNN	Benign	7.1e-7	T
MetaSVM	Benign	-0.88	T
PhyloP100		-7.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.030
MPC		0.63
ClinPred		0.0087	T
GERP RS		-8.3
gMVP		0.31
Mutation Taster		=98/2	polymorphism (auto)

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; COSMIC: COSV66570989; COSMIC: COSV66570989;