rs3129883

Variant names:

• chr6-32442360-T-C
• rs3129883
• NM_019111.5:c.83-88T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32442360-T-C
• chr6-32442360-T-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.83-88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,486,690 control chromosomes in the GnomAD database, including 421,895 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 0.74 (42115 hom., cov: 30)
  • Exomes 𝑓: 0.75 (379780 hom.)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 32 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.83-88T>C		intron_variant	Intron 1 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.83-88T>C		intron_variant	Intron 1 of 4	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.83-88T>C		intron_variant	Intron 1 of 4	6		ENSP00000364121.5
ENSG00000299747	ENST00000766007.1	n.163-4100A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112887 AN: 151752 Hom.: 42099 Cov.: 30

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.753 AC: 1005403 AN: 1334820 Hom.: 379780 AF XY: 0.755 AC XY: 502748 AN XY: 665796

African (AFR) AF: 0.714 AC: 22185 AN: 31082

American (AMR) AF: 0.762 AC: 32409 AN: 42528

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 19239 AN: 23262

East Asian (EAS) AF: 0.824 AC: 32176 AN: 39042

South Asian (SAS) AF: 0.794 AC: 61331 AN: 77254

European-Finnish (FIN) AF: 0.711 AC: 35591 AN: 50036

Middle Eastern (MID) AF: 0.820 AC: 4479 AN: 5464

European-Non Finnish (NFE) AF: 0.749 AC: 756163 AN: 1010004

Other (OTH) AF: 0.745 AC: 41830 AN: 56148

GnomAD4 genome AF: 0.744 AC: 112955 AN: 151870 Hom.: 42115 Cov.: 30 AF XY: 0.743 AC XY: 55166 AN XY: 74200

African (AFR) AF: 0.713 AC: 29506 AN: 41394

American (AMR) AF: 0.783 AC: 11959 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2898 AN: 3470

East Asian (EAS) AF: 0.827 AC: 4262 AN: 5156

South Asian (SAS) AF: 0.754 AC: 3629 AN: 4814

European-Finnish (FIN) AF: 0.710 AC: 7478 AN: 10526

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50694 AN: 67938

Other (OTH) AF: 0.781 AC: 1641 AN: 2102

Alfa AF: 0.752 Hom.: 42947

Bravo AF: 0.750

Asia WGS AF: 0.764 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-0.63
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: rs3129883; hg19: chr6-32410137;