rs7770370

chr6-33081144-A-Gchr6-33081144-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002121.6(HLA-DPB1):c.364+209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 585,394 control chromosomes in the GnomAD database, including 17,532 homozygotes. 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 0.27 (8243 hom., cov: 31)
  • Exomes 𝑓: 0.17 (9289 hom.)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

Genes affected

HLA-DPB1 (HGNC:4940): (major histocompatibility complex, class II, DP beta 1) HLA-DPB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta chain (DPB), 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 its gene contains 6 exons. Exon one 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 DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DPB1	NM_002121.6	c.364+209A>G		intron_variant		ENST00000418931.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.364+209A>G		intron_variant			NM_002121.6	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40650 AN: 151816 Hom.: 8220 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.170 AC: 73648 AN: 433460 Hom.: 9289 Cov.: 5 AF XY: 0.168 AC XY: 37815 AN XY: 225494

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.0930

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.268 AC: 40702 AN: 151934 Hom.: 8243 Cov.: 31 AF XY: 0.262 AC XY: 19470 AN XY: 74292

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0911

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.278

Alfa AF: 0.179 Hom.: 1626

Bravo AF: 0.290

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	6.0
Dann	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs7770370; hg19: chr6-33048921;