6-32442004-C-T

Variant names:

• chr6-32442004-C-T
• rs6931646
• NM_019111.5:c.83-444C>T

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.83-444C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,554 control chromosomes in the GnomAD database, including 18,582 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 0.49 (18582 hom., cov: 31)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 22 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	NM_019111.5	MANE Select	c.83-444C>T		intron	N/A	NP_061984.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	ENST00000395388.7	TSL:6 MANE Select	c.83-444C>T		intron	N/A	ENSP00000378786.2	P01903
	HLA-DRA	ENST00000870696.1		c.83-444C>T		intron	N/A	ENSP00000540755.1
	HLA-DRA	ENST00000917299.1		c.83-444C>T		intron	N/A	ENSP00000587358.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73815 AN: 151436 Hom.: 18572 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.524

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.487 AC: 73861 AN: 151554 Hom.: 18582 Cov.: 31 AF XY: 0.485 AC XY: 35891 AN XY: 74050

African (AFR) AF: 0.510 AC: 21046 AN: 41268

American (AMR) AF: 0.563 AC: 8582 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2369 AN: 3462

East Asian (EAS) AF: 0.660 AC: 3383 AN: 5124

South Asian (SAS) AF: 0.600 AC: 2885 AN: 4806

European-Finnish (FIN) AF: 0.293 AC: 3076 AN: 10506

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.455 AC: 30866 AN: 67832

Other (OTH) AF: 0.527 AC: 1110 AN: 2106

Alfa AF: 0.477 Hom.: 35376

Bravo AF: 0.511

Asia WGS AF: 0.596 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.28
DANN	Benign	0.63
PhyloP100		-0.98
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: rs6931646; hg19: chr6-32409781;