rs3129888

Variant names:

• chr6-32443949-G-A
• rs3129888
• NM_019111.5:c.*11+28G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 49 publications found

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]

ENSG00000299747 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019111.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	NM_019111.5	MANE Select	c.*11+28G>A		intron	N/A	NP_061984.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	ENST00000395388.7	TSL:6 MANE Select	c.*11+28G>A		intron	N/A	ENSP00000378786.2
	HLA-DRA	ENST00000374982.5	TSL:6	c.*11+28G>A		intron	N/A	ENSP00000364121.5
	ENSG00000299747	ENST00000766007.1		n.163-5689C>T		intron	N/A

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

GnomAD2 exomes AF: 0.821 AC: 145373 AN: 176966 AF XY: 0.830

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 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

African (AFR) AF: 0.794 AC: 23531 AN: 29652

American (AMR) AF: 0.791 AC: 24712 AN: 31224

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 18543 AN: 20590

East Asian (EAS) AF: 0.952 AC: 34750 AN: 36520

South Asian (SAS) AF: 0.961 AC: 60948 AN: 63420

European-Finnish (FIN) AF: 0.728 AC: 35840 AN: 49210

Middle Eastern (MID) AF: 0.903 AC: 4708 AN: 5212

European-Non Finnish (NFE) AF: 0.805 AC: 844016 AN: 1048520

Other (OTH) AF: 0.822 AC: 45415 AN: 55226

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

African (AFR) AF: 0.793 AC: 32881 AN: 41488

American (AMR) AF: 0.822 AC: 12565 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3155 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4998 AN: 5182

South Asian (SAS) AF: 0.965 AC: 4654 AN: 4824

European-Finnish (FIN) AF: 0.724 AC: 7628 AN: 10542

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54352 AN: 68002

Other (OTH) AF: 0.843 AC: 1778 AN: 2110

Alfa AF: 0.814 Hom.: 184757

Bravo AF: 0.814

Asia WGS AF: 0.927 AC: 3224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.47
DANN	Benign	0.61
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3129888; hg19: chr6-32411726;