6-33065074-T-C

Variant names:

• chr6-33065074-T-C
• rs8807
• ENST00000692443.1:c.*286A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000692443.1(HLA-DPA1):​c.*286A>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 0.16 in 151,784 control chromosomes in the GnomAD database, including 2,107 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 0.16 (2107 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DPA1 ENST00000692443.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 5 publications found

Genes affected

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPA1	NM_001242524.2	c.*286A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.*286A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001229454.1
HLA-DPA1	NM_033554.4	c.*286A>G		3_prime_UTR_variant	Exon 5 of 5		NP_291032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.*286A>G		3_prime_UTR_variant	Exon 5 of 5			ENSP00000509163.1
HLA-DPA1	ENST00000479107.1	n.4958A>G		non_coding_transcript_exon_variant	Exon 2 of 2	6
HLA-DPA1	ENST00000419277.5	c.*286A>G		3_prime_UTR_variant	Exon 6 of 6	6		ENSP00000393566.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24162 AN: 151666 Hom.: 2088 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.175

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.160 AC: 24213 AN: 151784 Hom.: 2107 Cov.: 32 AF XY: 0.162 AC XY: 11994 AN XY: 74182

African (AFR) AF: 0.210 AC: 8674 AN: 41328

American (AMR) AF: 0.143 AC: 2182 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3468

East Asian (EAS) AF: 0.147 AC: 758 AN: 5164

South Asian (SAS) AF: 0.205 AC: 985 AN: 4800

European-Finnish (FIN) AF: 0.142 AC: 1492 AN: 10522

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9002 AN: 67936

Other (OTH) AF: 0.175 AC: 369 AN: 2108

Alfa AF: 0.139 Hom.: 241

Bravo AF: 0.162

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.46
PhyloP100		-1.0
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: rs8807; hg19: chr6-33032851;