rs1042448

Variant names:

• chr6-33086565-T-A
• rs1042448
• NM_002121.6:c.*31T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-33086565-T-A
• chr6-33086565-T-C

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.*31T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 531,006 control chromosomes in the GnomAD database, including 24,847 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 0.37 (12062 hom., cov: 29)
  • Exomes 𝑓: 0.15 (12785 hom.)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 8 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 (REVEL=0.016).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*31T>A		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.*31T>A		3_prime_UTR_variant	Exon 6 of 6	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56341 AN: 150430 Hom.: 12040 Cov.: 29

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.00615 AC: 828 AN: 134740 AF XY: 0.00536

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.000131

Gnomad ASJ exome AF: 0.000862

Gnomad EAS exome AF: 0.00876

Gnomad FIN exome AF: 0.0136

Gnomad NFE exome AF: 0.00900

Gnomad OTH exome AF: 0.00227

GnomAD4 exome AF: 0.146 AC: 55722 AN: 380460 Hom.: 12785 Cov.: 0 AF XY: 0.140 AC XY: 28915 AN XY: 206336

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

African (AFR) AF: 0.355 AC: 3138 AN: 8850

American (AMR) AF: 0.0598 AC: 1652 AN: 27618

Ashkenazi Jewish (ASJ) AF: 0.0635 AC: 1029 AN: 16206

East Asian (EAS) AF: 0.437 AC: 6262 AN: 14340

South Asian (SAS) AF: 0.117 AC: 5409 AN: 46060

European-Finnish (FIN) AF: 0.111 AC: 3396 AN: 30716

Middle Eastern (MID) AF: 0.134 AC: 399 AN: 2984

European-Non Finnish (NFE) AF: 0.146 AC: 31054 AN: 213424

Other (OTH) AF: 0.167 AC: 3383 AN: 20262

⚠️ 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: 0.375 AC: 56390 AN: 150546 Hom.: 12062 Cov.: 29 AF XY: 0.367 AC XY: 27018 AN XY: 73578

African (AFR) AF: 0.561 AC: 22784 AN: 40630

American (AMR) AF: 0.296 AC: 4490 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3466

East Asian (EAS) AF: 0.630 AC: 3190 AN: 5060

South Asian (SAS) AF: 0.327 AC: 1558 AN: 4760

European-Finnish (FIN) AF: 0.247 AC: 2588 AN: 10498

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

European-Non Finnish (NFE) AF: 0.298 AC: 20142 AN: 67680

Other (OTH) AF: 0.383 AC: 792 AN: 2066

Alfa AF: 0.238 Hom.: 1070

Bravo AF: 0.389

Asia WGS AF: 0.480 AC: 1665 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	2.3
DANN	Benign	0.59
PhyloP100		-2.8
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: rs1042448; hg19: chr6-33054342; COSMIC: COSV69602356; COSMIC: COSV69602356;