rs3177928

Variant names:

• chr6-32444658-G-A
• rs3177928
• NM_019111.5:c.*18G>A

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.*18G>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 0.127 in 152,128 control chromosomes in the GnomAD database, including 1,424 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 (1424 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DRA NM_019111.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• Publications: 115 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 (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.*18G>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.*18G>A		3_prime_UTR_variant	Exon 5 of 5	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.*18G>A		3_prime_UTR_variant	Exon 5 of 5	6		ENSP00000364121.5
ENSG00000299747	ENST00000766007.1	n.163-6398C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19290 AN: 152010 Hom.: 1424 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.125

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.127 AC: 19306 AN: 152128 Hom.: 1424 Cov.: 32 AF XY: 0.130 AC XY: 9687 AN XY: 74364

African (AFR) AF: 0.0849 AC: 3524 AN: 41522

American (AMR) AF: 0.107 AC: 1643 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 214 AN: 3472

East Asian (EAS) AF: 0.0421 AC: 218 AN: 5174

South Asian (SAS) AF: 0.141 AC: 677 AN: 4818

European-Finnish (FIN) AF: 0.219 AC: 2308 AN: 10546

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10089 AN: 67988

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.129 Hom.: 4411

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	5.4
DANN	Benign	0.45
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3177928; hg19: chr6-32412435;