NM_019111.5:c.83-695G>A

Variant names:

• chr6-32441753-G-A
• rs3129882
• NM_019111.5:c.83-695G>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.83-695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,994 control chromosomes in the GnomAD database, including 23,495 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 0.55 (23495 hom., cov: 31)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 167 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 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.83-695G>A		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.83-695G>A		intron	N/A	ENSP00000378786.2	P01903
	HLA-DRA	ENST00000870696.1		c.83-695G>A		intron	N/A	ENSP00000540755.1
	HLA-DRA	ENST00000917299.1		c.83-695G>A		intron	N/A	ENSP00000587358.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83971 AN: 151876 Hom.: 23481 Cov.: 31

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.553 AC: 84019 AN: 151994 Hom.: 23495 Cov.: 31 AF XY: 0.549 AC XY: 40771 AN XY: 74304

African (AFR) AF: 0.556 AC: 23003 AN: 41408

American (AMR) AF: 0.543 AC: 8294 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1992 AN: 3466

East Asian (EAS) AF: 0.378 AC: 1950 AN: 5164

South Asian (SAS) AF: 0.458 AC: 2211 AN: 4828

European-Finnish (FIN) AF: 0.596 AC: 6304 AN: 10576

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38442 AN: 67950

Other (OTH) AF: 0.558 AC: 1178 AN: 2110

Alfa AF: 0.565 Hom.: 106803

Bravo AF: 0.557

Asia WGS AF: 0.425 AC: 1484 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.54
PhyloP100		1.5
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: rs3129882; hg19: chr6-32409530;