NM_002121.6:c.100+12A>G

Variant names:

• chr6-33076153-A-G
• rs2071351
• NM_002121.6:c.100+12A>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.100+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,571,896 control chromosomes in the GnomAD database, including 47,468 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 0.29 (8851 hom., cov: 32)
  • Exomes 𝑓: 0.21 (38617 hom.)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 32 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 (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.100+12A>G		intron_variant	Intron 1 of 5	ENST00000418931.7	NP_002112.3
HLA-DPA1	NM_001242524.2	c.-99-2484T>C		intron_variant	Intron 1 of 5		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.-23-2560T>C		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+12A>G		intron_variant	Intron 1 of 5	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44752 AN: 152004 Hom.: 8829 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.307

GnomAD2 exomes AF: 0.244 AC: 54444 AN: 222744 AF XY: 0.243

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.682

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.208 AC: 294801 AN: 1419774 Hom.: 38617 Cov.: 24 AF XY: 0.210 AC XY: 148106 AN XY: 706940

African (AFR) AF: 0.536 AC: 17584 AN: 32794

American (AMR) AF: 0.190 AC: 8107 AN: 42714

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 4553 AN: 25618

East Asian (EAS) AF: 0.635 AC: 24881 AN: 39178

South Asian (SAS) AF: 0.318 AC: 26504 AN: 83408

European-Finnish (FIN) AF: 0.102 AC: 5267 AN: 51544

Middle Eastern (MID) AF: 0.208 AC: 1183 AN: 5686

European-Non Finnish (NFE) AF: 0.178 AC: 192692 AN: 1079922

Other (OTH) AF: 0.238 AC: 14030 AN: 58910

GnomAD4 genome AF: 0.295 AC: 44815 AN: 152122 Hom.: 8851 Cov.: 32 AF XY: 0.292 AC XY: 21714 AN XY: 74392

African (AFR) AF: 0.514 AC: 21298 AN: 41456

American (AMR) AF: 0.246 AC: 3758 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3466

East Asian (EAS) AF: 0.688 AC: 3557 AN: 5168

South Asian (SAS) AF: 0.342 AC: 1649 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1088 AN: 10612

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12036 AN: 67988

Other (OTH) AF: 0.314 AC: 663 AN: 2114

Alfa AF: 0.242 Hom.: 7630

Bravo AF: 0.314

Asia WGS AF: 0.456 AC: 1583 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	7.3
DANN	Benign	0.53
PhyloP100		0.38
PromoterAI		0.0066	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: rs2071351; hg19: chr6-33043930; COSMIC: COSV69602537; COSMIC: COSV69602537;