NM_019111.5:c.83-983C>A

Variant names:

• chr6-32441465-C-A
• rs3135392
• NM_019111.5:c.83-983C>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.83-983C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,056 control chromosomes in the GnomAD database, including 11,488 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 0.38 (11488 hom., cov: 32)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• Publications: 36 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 (NFE) allele frequency at 95% confidence interval = 0.385 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.83-983C>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.83-983C>A		intron	N/A	ENSP00000378786.2
	HLA-DRA	ENST00000870696.1		c.83-983C>A		intron	N/A	ENSP00000540755.1
	HLA-DRA	ENST00000917299.1		c.83-983C>A		intron	N/A	ENSP00000587358.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57891 AN: 151938 Hom.: 11469 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.381 AC: 57955 AN: 152056 Hom.: 11488 Cov.: 32 AF XY: 0.386 AC XY: 28651 AN XY: 74314

African (AFR) AF: 0.369 AC: 15310 AN: 41442

American (AMR) AF: 0.340 AC: 5198 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 817 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1475 AN: 5172

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4826

European-Finnish (FIN) AF: 0.573 AC: 6049 AN: 10550

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26455 AN: 67982

Other (OTH) AF: 0.370 AC: 782 AN: 2116

Alfa AF: 0.382 Hom.: 28248

Bravo AF: 0.366

Asia WGS AF: 0.323 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.29
PhyloP100		-0.74
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: rs3135392; hg19: chr6-32409242;