rs9348904

Variant names:

• chr6-33073058-A-G
• rs9348904
• ENST00000692443.1:c.100+413T>C

Variant summary

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

The ENST00000692443.1(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 ENST00000692443.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 16 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=-0.92).
• 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 rank	MANE	Protein	UniProt
HLA-DPA1	NM_001242524.2	c.100+413T>C		intron_variant	Intron 2 of 5		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.100+413T>C		intron_variant	Intron 2 of 5		NP_001229454.1
HLA-DPA1	NM_001405020.1	c.100+413T>C		intron_variant	Intron 1 of 3		NP_001391949.1
HLA-DPA1	NM_033554.4	c.100+413T>C		intron_variant	Intron 1 of 4		NP_291032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.100+413T>C		intron_variant	Intron 1 of 4			ENSP00000509163.1

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

African (AFR) AF: 0.494 AC: 20472 AN: 41428

American (AMR) AF: 0.245 AC: 3745 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3466

East Asian (EAS) AF: 0.689 AC: 3565 AN: 5176

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4816

European-Finnish (FIN) AF: 0.103 AC: 1091 AN: 10590

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12029 AN: 67998

Other (OTH) AF: 0.311 AC: 656 AN: 2112

Alfa AF: 0.261 Hom.: 4876

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
PhyloP100		-2.4
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: rs9348904; hg19: chr6-33040835;