rs3135021

Variant names:

• chr6-33077781-G-A
• rs3135021
• NM_002121.6:c.100+1640G>A

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.100+1640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,916 control chromosomes in the GnomAD database, including 7,983 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 0.32 (7983 hom., cov: 31)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 46 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]

HLA-DPA1 (HGNC:4938): (major histocompatibility complex, class II, DP alpha 1) HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, 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 alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and 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 (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.100+1640G>A		intron_variant	Intron 1 of 5	ENST00000418931.7	NP_002112.3
HLA-DPA1	NM_001242524.2	c.-100+2899C>T		intron_variant	Intron 1 of 5		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.-24+2899C>T		intron_variant	Intron 1 of 5		NP_001229454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.100+1640G>A		intron_variant	Intron 1 of 5	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48091 AN: 151798 Hom.: 7959 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.317 AC: 48158 AN: 151916 Hom.: 7983 Cov.: 31 AF XY: 0.324 AC XY: 24080 AN XY: 74256

African (AFR) AF: 0.329 AC: 13637 AN: 41406

American (AMR) AF: 0.414 AC: 6332 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1101 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1277 AN: 5168

South Asian (SAS) AF: 0.405 AC: 1951 AN: 4822

European-Finnish (FIN) AF: 0.367 AC: 3872 AN: 10538

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19049 AN: 67924

Other (OTH) AF: 0.327 AC: 691 AN: 2110

Alfa AF: 0.301 Hom.: 8960

Bravo AF: 0.323

Asia WGS AF: 0.374 AC: 1300 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	3.1
DANN	Benign	0.30
PhyloP100		-0.076
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: rs3135021; hg19: chr6-33045558;