rs3077

Positions:

• chr6-33065245-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242525.2(HLA-DPA1):​c.*115T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,222 control chromosomes in the GnomAD database, including 8,455 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 (8455 hom., cov: 32)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: HLA-DPA1 NM_001242525.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DPA1	NM_033554.4	c.*115T>C		3_prime_UTR_variant	5/5	ENST00000692443.1	NP_291032.2
HLA-DPA1	NM_001242525.2	c.*115T>C		3_prime_UTR_variant	6/6		NP_001229454.1
HLA-DPA1	NM_001242524.2	c.*115T>C		3_prime_UTR_variant	6/6		NP_001229453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.*115T>C		3_prime_UTR_variant	5/5		NM_033554.4	ENSP00000509163	P1
HLA-DPA1	ENST00000419277.5	c.*115T>C		3_prime_UTR_variant	6/6			ENSP00000393566	P1
HLA-DPA1	ENST00000479107.1	n.4787T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44035 AN: 151970 Hom.: 8436 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.119 AC: 16 AN: 134 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 12 AN XY: 96

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.290 AC: 44085 AN: 152088 Hom.: 8455 Cov.: 32 AF XY: 0.287 AC XY: 21366 AN XY: 74358

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.309

Alfa AF: 0.204 Hom.: 7222

Bravo AF: 0.308

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs3077; hg19: chr6-33033022;