rs13218331

Positions:

• chr6-32443585-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019111.5(HLA-DRA):​c.610+119A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,142,124 control chromosomes in the GnomAD database, including 12,656 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 0.13 (1432 hom., cov: 32)
  • Exomes 𝑓: 0.14 (11224 hom.)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.610+119A>C		intron_variant		ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.610+119A>C		intron_variant			NM_019111.5	ENSP00000378786	P1
HLA-DRA	ENST00000374982.5	c.535+119A>C		intron_variant				ENSP00000364121

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19324 AN: 152082 Hom.: 1432 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.144 AC: 142097 AN: 989924 Hom.: 11224 Cov.: 13 AF XY: 0.142 AC XY: 71140 AN XY: 499274

Gnomad4 AFR exome AF: 0.0848

Gnomad4 AMR exome AF: 0.0796

Gnomad4 ASJ exome AF: 0.0556

Gnomad4 EAS exome AF: 0.0529

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.127 AC: 19340 AN: 152200 Hom.: 1432 Cov.: 32 AF XY: 0.130 AC XY: 9706 AN XY: 74410

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0616

Gnomad4 EAS AF: 0.0422

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.123

Alfa AF: 0.127 Hom.: 635

Bravo AF: 0.116

Asia WGS AF: 0.0970 AC: 341 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	0.62
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs13218331; hg19: chr6-32411362;