chr6-33069410-C-G

Position:

• chr6-33069410-C-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.347-110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,158,104 control chromosomes in the GnomAD database, including 29,791 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 (8535 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21256 hom.)
• Consequence: HLA-DPA1 NM_001242525.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DPA1	NM_033554.4	c.347-110G>C		intron_variant		ENST00000692443.1
HLA-DPA1	NM_001242525.2	c.347-110G>C		intron_variant
HLA-DPA1	NM_001242524.2	c.347-110G>C		intron_variant
HLA-DPA1	NM_001405020.1	c.347-110G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.347-110G>C		intron_variant			NM_033554.4	P1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44297 AN: 151918 Hom.: 8516 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.170 AC: 170691 AN: 1006066 Hom.: 21256 Cov.: 14 AF XY: 0.175 AC XY: 88767 AN XY: 507092

Gnomad4 AFR exome AF: 0.456

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.292 AC: 44348 AN: 152038 Hom.: 8535 Cov.: 32 AF XY: 0.289 AC XY: 21486 AN XY: 74316

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.313

Alfa AF: 0.0859 Hom.: 109

Bravo AF: 0.310

Asia WGS AF: 0.460 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.5
DANN	Benign	0.72

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: rs3830066; hg19: chr6-33037187;