NM_002121.6:c.*146A>G

Variant names:

• chr6-33086680-A-G
• rs1042544
• NM_002121.6:c.*146A>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.*146A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 396,756 control chromosomes in the GnomAD database, including 16,843 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 0.38 (12402 hom., cov: 31)
  • Exomes 𝑓: 0.11 (4441 hom.)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 23 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*146A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.*146A>G		3_prime_UTR_variant	Exon 6 of 6	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57572 AN: 151682 Hom.: 12380 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.105 AC: 25793 AN: 244956 Hom.: 4441 Cov.: 0 AF XY: 0.103 AC XY: 14093 AN XY: 136350

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.170 AC: 703 AN: 4140

American (AMR) AF: 0.0360 AC: 768 AN: 21306

Ashkenazi Jewish (ASJ) AF: 0.0407 AC: 405 AN: 9942

East Asian (EAS) AF: 0.248 AC: 1158 AN: 4672

South Asian (SAS) AF: 0.0896 AC: 3692 AN: 41200

European-Finnish (FIN) AF: 0.116 AC: 2473 AN: 21240

Middle Eastern (MID) AF: 0.203 AC: 524 AN: 2576

European-Non Finnish (NFE) AF: 0.113 AC: 14549 AN: 128228

Other (OTH) AF: 0.131 AC: 1521 AN: 11652

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.380 AC: 57621 AN: 151800 Hom.: 12402 Cov.: 31 AF XY: 0.373 AC XY: 27677 AN XY: 74248

African (AFR) AF: 0.568 AC: 23437 AN: 41238

American (AMR) AF: 0.299 AC: 4576 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3468

East Asian (EAS) AF: 0.639 AC: 3303 AN: 5170

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4814

European-Finnish (FIN) AF: 0.252 AC: 2667 AN: 10588

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20331 AN: 67928

Other (OTH) AF: 0.392 AC: 827 AN: 2108

Alfa AF: 0.335 Hom.: 17777

Bravo AF: 0.390

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.40
PhyloP100		-0.12
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: rs1042544; hg19: chr6-33054457; COSMIC: COSV69602312; COSMIC: COSV69602312;