chr6-33081144-A-G

Variant names:

• chr6-33081144-A-G
• rs7770370
• NM_002121.6:c.364+209A>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+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
• Publications: 25 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002121.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	NM_002121.6	MANE Select	c.364+209A>G		intron	N/A	NP_002112.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.364+209A>G		intron	N/A	ENSP00000408146.2
	HLA-DPB1	ENST00000469120.1	TSL:6	n.605A>G		non_coding_transcript_exon	Exon 2 of 2
	HLA-DPB1	ENST00000478189.1	TSL:6	n.204A>G		non_coding_transcript_exon	Exon 1 of 3

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

African (AFR) AF: 0.542 AC: 6366 AN: 11746

American (AMR) AF: 0.158 AC: 2418 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 1432 AN: 12792

East Asian (EAS) AF: 0.456 AC: 13411 AN: 29404

South Asian (SAS) AF: 0.171 AC: 5818 AN: 34060

European-Finnish (FIN) AF: 0.0930 AC: 2606 AN: 28030

Middle Eastern (MID) AF: 0.120 AC: 228 AN: 1900

European-Non Finnish (NFE) AF: 0.133 AC: 36502 AN: 275290

Other (OTH) AF: 0.195 AC: 4867 AN: 24930

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

African (AFR) AF: 0.548 AC: 22646 AN: 41326

American (AMR) AF: 0.181 AC: 2765 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3472

East Asian (EAS) AF: 0.542 AC: 2785 AN: 5134

South Asian (SAS) AF: 0.197 AC: 951 AN: 4822

European-Finnish (FIN) AF: 0.0911 AC: 967 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9508 AN: 67962

Other (OTH) AF: 0.278 AC: 586 AN: 2106

Alfa AF: 0.176 Hom.: 2509

Bravo AF: 0.290

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.0
DANN	Benign	0.24
PhyloP100		-0.094
PromoterAI		0.017	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: rs7770370; hg19: chr6-33048921;