6-32444069-C-G

Variant names:

• chr6-32444069-C-G
• rs2239802
• NM_019111.5:c.*11+148C>G

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+148C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 511,156 control chromosomes in the GnomAD database, including 153,196 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 0.77 (44948 hom., cov: 31)
  • Exomes 𝑓: 0.77 (108248 hom.)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350
• Publications: 44 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.*11+148C>G		intron_variant	Intron 4 of 4	ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.*11+148C>G		intron_variant	Intron 4 of 4	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.*11+148C>G		intron_variant	Intron 4 of 4	6		ENSP00000364121.5
ENSG00000299747	ENST00000766007.1	n.163-5809G>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116661 AN: 151994 Hom.: 44933 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.773 AC: 277676 AN: 359044 Hom.: 108248 AF XY: 0.775 AC XY: 140847 AN XY: 181712

African (AFR) AF: 0.708 AC: 6464 AN: 9124

American (AMR) AF: 0.791 AC: 7216 AN: 9118

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 8706 AN: 10418

East Asian (EAS) AF: 0.815 AC: 19507 AN: 23938

South Asian (SAS) AF: 0.826 AC: 8698 AN: 10524

European-Finnish (FIN) AF: 0.725 AC: 17714 AN: 24448

Middle Eastern (MID) AF: 0.807 AC: 1294 AN: 1604

European-Non Finnish (NFE) AF: 0.771 AC: 191892 AN: 249018

Other (OTH) AF: 0.776 AC: 16185 AN: 20852

GnomAD4 genome AF: 0.767 AC: 116728 AN: 152112 Hom.: 44948 Cov.: 31 AF XY: 0.766 AC XY: 56968 AN XY: 74348

African (AFR) AF: 0.716 AC: 29724 AN: 41498

American (AMR) AF: 0.796 AC: 12167 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2951 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4308 AN: 5174

South Asian (SAS) AF: 0.812 AC: 3906 AN: 4812

European-Finnish (FIN) AF: 0.723 AC: 7634 AN: 10562

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53303 AN: 67992

Other (OTH) AF: 0.798 AC: 1688 AN: 2114

Alfa AF: 0.783 Hom.: 22584

Bravo AF: 0.773

Asia WGS AF: 0.783 AC: 2725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.63
PhyloP100		0.35
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: rs2239802; hg19: chr6-32411846;