NM_002121.6:c.100+1780G>A

Variant names:

• chr6-33077921-G-A
• rs7750458
• NM_002121.6:c.100+1780G>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+1780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,202 control chromosomes in the GnomAD database, including 790 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 0.097 (790 hom., cov: 31)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.100+1780G>A		intron_variant	Intron 1 of 5	ENST00000418931.7	NP_002112.3
HLA-DPA1	NM_001242524.2	c.-100+2759C>T		intron_variant	Intron 1 of 5		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.-24+2759C>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+1780G>A		intron_variant	Intron 1 of 5	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14820 AN: 152084 Hom.: 790 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.0974 AC: 14827 AN: 152202 Hom.: 790 Cov.: 31 AF XY: 0.0976 AC XY: 7262 AN XY: 74440

African (AFR) AF: 0.122 AC: 5079 AN: 41492

American (AMR) AF: 0.136 AC: 2086 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3470

East Asian (EAS) AF: 0.0880 AC: 456 AN: 5180

South Asian (SAS) AF: 0.149 AC: 720 AN: 4822

European-Finnish (FIN) AF: 0.0284 AC: 302 AN: 10616

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5206 AN: 68012

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.0829 Hom.: 1120

Bravo AF: 0.105

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.49
PhyloP100		0.28
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: rs7750458; hg19: chr6-33045698;