6-32444069-C-G

Position:

• chr6-32444069-C-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.*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

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=-0.88).
• 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/exons	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.*11+148C>G		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.*11+148C>G		intron_variant		6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.*11+148C>G		intron_variant		6		ENSP00000364121.5

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

Gnomad4 AFR exome AF: 0.708

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.836

Gnomad4 EAS exome AF: 0.815

Gnomad4 SAS exome AF: 0.826

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.771

Gnomad4 OTH exome AF: 0.776

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

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.798

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

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: rs2239802; hg19: chr6-32411846;