rs1051336

Positions:

• chr6-32444815-G-A
• chr6-32444815-G-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.*175G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 153,648 control chromosomes in the GnomAD database, including 1,899 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 0.15 (1894 hom., cov: 31)
  • Exomes 𝑓: 0.083 (5 hom.)
• Consequence: HLA-DRA NM_019111.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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 = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.*175G>A		3_prime_UTR_variant	5/5	ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.*175G>A		3_prime_UTR_variant	5/5	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.*175G>A		3_prime_UTR_variant	5/5	6		ENSP00000364121.5

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23107 AN: 151966 Hom.: 1897 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0831 AC: 130 AN: 1564 Hom.: 5 Cov.: 0 AF XY: 0.0876 AC XY: 69 AN XY: 788

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.0286

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0500

GnomAD4 genome AF: 0.152 AC: 23113 AN: 152084 Hom.: 1894 Cov.: 31 AF XY: 0.150 AC XY: 11120 AN XY: 74350

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0689

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.148

Alfa AF: 0.166 Hom.: 808

Bravo AF: 0.146

Asia WGS AF: 0.0900 AC: 313 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	2.6
DANN	Benign	0.51

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: rs1051336; hg19: chr6-32412592;