6-33068400-A-G

Position:

• chr6-33068400-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001405020.1(HLA-DPA1):​c.*250T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 433,916 control chromosomes in the GnomAD database, including 20,149 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 (10914 hom., cov: 32)
  • Exomes 𝑓: 0.21 (9235 hom.)
• Consequence: HLA-DPA1 NM_001405020.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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]

HLA-DPA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HLA-DPA1	NM_001405020.1	c.*250T>C		3_prime_UTR_variant	4/4		NP_001391949.1
HLA-DPA1	NM_001242524.2	c.*12+238T>C		intron_variant			NP_001229453.1
HLA-DPA1	NM_001242525.2	c.*12+238T>C		intron_variant			NP_001229454.1
HLA-DPA1	NM_033554.4	c.*12+238T>C		intron_variant			NP_291032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.*12+238T>C		intron_variant				ENSP00000509163.1
HLA-DPA1	ENST00000437811.1	c.*250T>C		3_prime_UTR_variant	2/2	6		ENSP00000405500.1
HLA-DPA1	ENST00000419277.5	c.*12+238T>C		intron_variant		6		ENSP00000393566.1
HLA-DPA1	ENST00000479107.1	n.1632T>C		non_coding_transcript_exon_variant	2/2	6

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48587 AN: 151950 Hom.: 10866 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: 0.345

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.207 AC: 58319 AN: 281848 Hom.: 9235 Cov.: 2 AF XY: 0.206 AC XY: 29599 AN XY: 143944

Gnomad4 AFR exome AF: 0.577

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.0790

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.320 AC: 48693 AN: 152068 Hom.: 10914 Cov.: 32 AF XY: 0.317 AC XY: 23575 AN XY: 74362

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.336

Alfa AF: 0.235 Hom.: 1943

Bravo AF: 0.344

Asia WGS AF: 0.462 AC: 1605 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	7.9
DANN	Benign	0.61

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: rs3180554; hg19: chr6-33036177;