rs987870

Positions:

• chr6-33075103-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.-23-1510T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,136 control chromosomes in the GnomAD database, including 3,456 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 0.19 (3456 hom., cov: 32)
• Consequence: HLA-DPA1 NM_001242525.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DPA1	NM_001242525.2	c.-23-1510T>C		intron_variant			NP_001229454.1
HLA-DPA1	NM_001242524.2	c.-99-1434T>C		intron_variant			NP_001229453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000417724.1	c.-140-1393T>C		intron_variant				ENSP00000398134
HLA-DPA1	ENST00000419277.5	c.-99-1434T>C		intron_variant				ENSP00000393566	P1
HLA-DPA1	ENST00000453337.1	c.-202-1331T>C		intron_variant				ENSP00000390929
HLA-DPA1	ENST00000476642.5	n.77-5217T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29352 AN: 152018 Hom.: 3459 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29362 AN: 152136 Hom.: 3456 Cov.: 32 AF XY: 0.189 AC XY: 14042 AN XY: 74380

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.203

Alfa AF: 0.148 Hom.: 3314

Bravo AF: 0.202

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.89

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: rs987870; hg19: chr6-33042880;