chr6-33065198-T-C

Variant names:

• chr6-33065198-T-C
• rs7905
• ENST00000692443:c.*162A>G

Variant summary

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

The NM_033554.4(HLA-DPA1):​c.*162A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,058 control chromosomes in the GnomAD database, including 3,976 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 0.21 (3976 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DPA1 NM_033554.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPA1	NM_001242524.2	c.*162A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.*162A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001229454.1
HLA-DPA1	NM_033554.4	c.*162A>G		3_prime_UTR_variant	Exon 5 of 5		NP_291032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443	c.*162A>G		3_prime_UTR_variant	Exon 5 of 5			ENSP00000509163.1
HLA-DPA1	ENST00000419277	c.*162A>G		3_prime_UTR_variant	Exon 6 of 6			ENSP00000393566.1
HLA-DPA1	ENST00000479107.1	n.4834A>G		non_coding_transcript_exon_variant	Exon 2 of 2	6

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31595 AN: 151940 Hom.: 3975 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.219

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.208 AC: 31610 AN: 152058 Hom.: 3976 Cov.: 32 AF XY: 0.204 AC XY: 15173 AN XY: 74334

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.0779

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.217

Alfa AF: 0.150 Hom.: 2493

Bravo AF: 0.217

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.4
DANN	Benign	0.27

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: rs7905; hg19: chr6-33032975;