chr6-33067099-T-C

Variant names:

• chr6-33067099-T-C
• rs9469332
• ENST00000692443.1:c.*12+1539A>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.*12+1539A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,008 control chromosomes in the GnomAD database, including 10,911 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 0.32 (10911 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DPA1 ENST00000692443.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPA1	NM_001242524.2	c.*12+1539A>G		intron_variant	Intron 5 of 5		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.*12+1539A>G		intron_variant	Intron 5 of 5		NP_001229454.1
HLA-DPA1	NM_033554.4	c.*12+1539A>G		intron_variant	Intron 4 of 4		NP_291032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.*12+1539A>G		intron_variant	Intron 4 of 4			ENSP00000509163.1
HLA-DPA1	ENST00000479107.1	n.2933A>G		non_coding_transcript_exon_variant	Exon 2 of 2	6
HLA-DPA1	ENST00000419277.5	c.*12+1539A>G		intron_variant	Intron 5 of 5	6		ENSP00000393566.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48556 AN: 151890 Hom.: 10863 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.330

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

GnomAD4 genome AF: 0.320 AC: 48662 AN: 152008 Hom.: 10911 Cov.: 32 AF XY: 0.317 AC XY: 23551 AN XY: 74312

African (AFR) AF: 0.601 AC: 24863 AN: 41386

American (AMR) AF: 0.259 AC: 3963 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3468

East Asian (EAS) AF: 0.688 AC: 3549 AN: 5162

South Asian (SAS) AF: 0.343 AC: 1653 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1090 AN: 10602

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12013 AN: 67976

Other (OTH) AF: 0.336 AC: 710 AN: 2112

Alfa AF: 0.285 Hom.: 8107

Bravo AF: 0.344

Asia WGS AF: 0.462 AC: 1606 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	8.2
DANN	Benign	0.75
PhyloP100		-0.69
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: rs9469332; hg19: chr6-33034876;