rs9348904

chr6-33073058-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.100+413T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,082 control chromosomes in the GnomAD database, including 8,408 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 (8408 hom., cov: 32)
• Consequence: HLA-DPA1 NM_001242525.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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=-0.92).
• 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	UniProt
HLA-DPA1	NM_033554.4	c.100+413T>C		intron_variant		ENST00000692443.1
HLA-DPA1	NM_001242525.2	c.100+413T>C		intron_variant
HLA-DPA1	NM_001242524.2	c.100+413T>C		intron_variant
HLA-DPA1	NM_001405020.1	c.100+413T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.100+413T>C		intron_variant			NM_033554.4	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43926 AN: 151964 Hom.: 8392 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.289 AC: 43973 AN: 152082 Hom.: 8408 Cov.: 32 AF XY: 0.287 AC XY: 21305 AN XY: 74346

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.311

Alfa AF: 0.212 Hom.: 1264

Bravo AF: 0.308

Asia WGS AF: 0.451 AC: 1568 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	0.33
Dann	Benign	0.25

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: rs9348904; hg19: chr6-33040835;