rs1041885

Variant names:

• chr6-32445032-T-A
• rs1041885
• NM_019111.5:c.*392T>A

Variant summary

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

The NM_019111.5(HLA-DRA):​c.*392T>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 152,962 control chromosomes in the GnomAD database, including 1,879 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 (1869 hom., cov: 28)
  • Exomes 𝑓: 0.088 (10 hom.)
• Consequence: HLA-DRA NM_019111.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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 = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.*392T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.*392T>A		3_prime_UTR_variant	Exon 5 of 5	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.*392T>A		3_prime_UTR_variant	Exon 5 of 5	6		ENSP00000364121.5

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22870 AN: 150820 Hom.: 1872 Cov.: 28

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.0879 AC: 178 AN: 2024 Hom.: 10 Cov.: 0 AF XY: 0.0935 AC XY: 95 AN XY: 1016

Gnomad4 AFR exome AF: 0.0909

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.0233

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.0667

GnomAD4 genome AF: 0.152 AC: 22876 AN: 150938 Hom.: 1869 Cov.: 28 AF XY: 0.149 AC XY: 10966 AN XY: 73626

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0664

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.147

Alfa AF: 0.172 Hom.: 1358

Bravo AF: 0.146

Asia WGS AF: 0.0890 AC: 311 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	8.7
DANN	Benign	0.52

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: rs1041885; hg19: chr6-32412809;