6-33081160-C-G

Variant names:

• chr6-33081160-C-G
• rs7770501
• NM_002121.6:c.364+225C>G

Variant summary

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

The NM_002121.6(HLA-DPB1):​c.364+225C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 551,524 control chromosomes in the GnomAD database, including 11,191 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 0.20 (4742 hom., cov: 31)
  • Exomes 𝑓: 0.14 (6449 hom.)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.364+225C>G		intron_variant	Intron 2 of 5	ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.364+225C>G		intron_variant	Intron 2 of 5	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30929 AN: 151750 Hom.: 4726 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0475

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.140 AC: 56037 AN: 399656 Hom.: 6449 Cov.: 5 AF XY: 0.138 AC XY: 28633 AN XY: 207690

African (AFR) AF: 0.401 AC: 4417 AN: 11012

American (AMR) AF: 0.115 AC: 1636 AN: 14212

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 610 AN: 12224

East Asian (EAS) AF: 0.441 AC: 12617 AN: 28578

South Asian (SAS) AF: 0.138 AC: 4060 AN: 29474

European-Finnish (FIN) AF: 0.0813 AC: 2208 AN: 27160

Middle Eastern (MID) AF: 0.0723 AC: 132 AN: 1826

European-Non Finnish (NFE) AF: 0.106 AC: 26735 AN: 251558

Other (OTH) AF: 0.153 AC: 3622 AN: 23612

GnomAD4 genome AF: 0.204 AC: 30967 AN: 151868 Hom.: 4742 Cov.: 31 AF XY: 0.200 AC XY: 14811 AN XY: 74228

African (AFR) AF: 0.397 AC: 16404 AN: 41318

American (AMR) AF: 0.129 AC: 1966 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 165 AN: 3472

East Asian (EAS) AF: 0.512 AC: 2629 AN: 5134

South Asian (SAS) AF: 0.160 AC: 770 AN: 4816

European-Finnish (FIN) AF: 0.0780 AC: 825 AN: 10572

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7673 AN: 67952

Other (OTH) AF: 0.213 AC: 450 AN: 2112

Alfa AF: 0.0643 Hom.: 90

Bravo AF: 0.218

Asia WGS AF: 0.298 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		-2.0
PromoterAI		0.0030	Neutral
Mutation Taster		=100/0	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: rs7770501; hg19: chr6-33048937;