rs3129888

chr6-32443949-G-A

Variant summary

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

The NM_019111.5(HLA-DRA):c.*11+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,491,692 control chromosomes in the GnomAD database, including 497,078 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 0.81 (50032 hom., cov: 31)
  • Exomes 𝑓: 0.82 (447046 hom.)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRA	NM_019111.5	c.*11+28G>A		intron_variant		ENST00000395388.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.*11+28G>A		intron_variant			NM_019111.5	P1
HLA-DRA	ENST00000374982.5	c.*11+28G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123004 AN: 152000 Hom.: 50015 Cov.: 31

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.965

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.842

GnomAD3 exomes AF: 0.821 AC: 145373 AN: 176966 Hom.: 60226 AF XY: 0.830 AC XY: 79544 AN XY: 95828

Gnomad AFR exome AF: 0.788

Gnomad AMR exome AF: 0.777

Gnomad ASJ exome AF: 0.901

Gnomad EAS exome AF: 0.967

Gnomad SAS exome AF: 0.962

Gnomad FIN exome AF: 0.724

Gnomad NFE exome AF: 0.803

Gnomad OTH exome AF: 0.816

GnomAD4 exome AF: 0.816 AC: 1092463 AN: 1339574 Hom.: 447046 Cov.: 23 AF XY: 0.819 AC XY: 538708 AN XY: 657588

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.901

Gnomad4 EAS exome AF: 0.952

Gnomad4 SAS exome AF: 0.961

Gnomad4 FIN exome AF: 0.728

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.822

GnomAD4 genome AF: 0.809 AC: 123073 AN: 152118 Hom.: 50032 Cov.: 31 AF XY: 0.809 AC XY: 60114 AN XY: 74340

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.965

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.843

Alfa AF: 0.820 Hom.: 72488

Bravo AF: 0.814

Asia WGS AF: 0.927 AC: 3224 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	0.47
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: rs3129888; hg19: chr6-32411726;