rs3129883

Positions:

• chr6-32442360-T-C
• chr6-32442360-T-G

Variant summary

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

The NM_019111.5(HLA-DRA):​c.83-88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,486,690 control chromosomes in the GnomAD database, including 421,895 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 0.74 (42115 hom., cov: 30)
  • Exomes 𝑓: 0.75 (379780 hom.)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

Genes affected

HLA-DRA (HGNC:4947): (major histocompatibility complex, class II, DR alpha) HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. This molecule is expressed on the surface of various antigen presenting cells such as B lymphocytes, dendritic cells, and monocytes/macrophages, and plays a central role in the immune system and response by presenting peptides derived from extracellular proteins, in particular, pathogen-derived peptides to T cells. The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.83-88T>C		intron_variant		ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.83-88T>C		intron_variant			NM_019111.5	ENSP00000378786	P1
HLA-DRA	ENST00000374982.5	c.83-88T>C		intron_variant				ENSP00000364121

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112887 AN: 151752 Hom.: 42099 Cov.: 30

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.753 AC: 1005403 AN: 1334820 Hom.: 379780 AF XY: 0.755 AC XY: 502748 AN XY: 665796

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.762

Gnomad4 ASJ exome AF: 0.827

Gnomad4 EAS exome AF: 0.824

Gnomad4 SAS exome AF: 0.794

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.749

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.744 AC: 112955 AN: 151870 Hom.: 42115 Cov.: 30 AF XY: 0.743 AC XY: 55166 AN XY: 74200

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.781

Alfa AF: 0.752 Hom.: 24919

Bravo AF: 0.750

Asia WGS AF: 0.764 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.67

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: rs3129883; hg19: chr6-32410137;