6-32444056-C-T

Variant names:

• chr6-32444056-C-T
• rs2239803
• NM_019111.5:c.*11+135C>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.*11+135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 578,398 control chromosomes in the GnomAD database, including 67,925 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 0.50 (19823 hom., cov: 32)
  • Exomes 𝑓: 0.46 (48102 hom.)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 38 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.*11+135C>T		intron_variant	Intron 4 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.*11+135C>T		intron_variant	Intron 4 of 4	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.*11+135C>T		intron_variant	Intron 4 of 4	6		ENSP00000364121.5
ENSG00000299747	ENST00000766007.1	n.163-5796G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76225 AN: 151946 Hom.: 19812 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.463 AC: 197461 AN: 426334 Hom.: 48102 AF XY: 0.468 AC XY: 100574 AN XY: 214722

African (AFR) AF: 0.509 AC: 5364 AN: 10546

American (AMR) AF: 0.573 AC: 5636 AN: 9838

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 7526 AN: 10960

East Asian (EAS) AF: 0.573 AC: 14169 AN: 24746

South Asian (SAS) AF: 0.656 AC: 8853 AN: 13504

European-Finnish (FIN) AF: 0.310 AC: 8230 AN: 26520

Middle Eastern (MID) AF: 0.675 AC: 1205 AN: 1784

European-Non Finnish (NFE) AF: 0.442 AC: 134956 AN: 305318

Other (OTH) AF: 0.498 AC: 11522 AN: 23118

GnomAD4 genome AF: 0.502 AC: 76270 AN: 152064 Hom.: 19823 Cov.: 32 AF XY: 0.500 AC XY: 37178 AN XY: 74330

African (AFR) AF: 0.528 AC: 21898 AN: 41468

American (AMR) AF: 0.577 AC: 8828 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2434 AN: 3470

East Asian (EAS) AF: 0.682 AC: 3525 AN: 5170

South Asian (SAS) AF: 0.649 AC: 3124 AN: 4810

European-Finnish (FIN) AF: 0.305 AC: 3224 AN: 10568

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31524 AN: 67974

Other (OTH) AF: 0.547 AC: 1154 AN: 2110

Alfa AF: 0.490 Hom.: 72515

Bravo AF: 0.524

Asia WGS AF: 0.637 AC: 2219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.41
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: rs2239803; hg19: chr6-32411833;