rs13218331

Variant names:

• chr6-32443585-A-C
• rs13218331
• NM_019111.5:c.610+119A>C

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.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
• Publications: 14 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.610+119A>C		intron_variant	Intron 3 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.610+119A>C		intron_variant	Intron 3 of 4	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.535+119A>C		intron_variant	Intron 3 of 4	6		ENSP00000364121.5
ENSG00000299747	ENST00000766007.1	n.163-5325T>G		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.0848 AC: 1949 AN: 22980

American (AMR) AF: 0.0796 AC: 2398 AN: 30144

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 991 AN: 17826

East Asian (EAS) AF: 0.0529 AC: 1957 AN: 37012

South Asian (SAS) AF: 0.135 AC: 8404 AN: 62210

European-Finnish (FIN) AF: 0.214 AC: 10394 AN: 48578

Middle Eastern (MID) AF: 0.0684 AC: 313 AN: 4576

European-Non Finnish (NFE) AF: 0.152 AC: 109911 AN: 722908

Other (OTH) AF: 0.132 AC: 5780 AN: 43690

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

African (AFR) AF: 0.0850 AC: 3528 AN: 41520

American (AMR) AF: 0.108 AC: 1645 AN: 15296

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

East Asian (EAS) AF: 0.0422 AC: 218 AN: 5170

South Asian (SAS) AF: 0.141 AC: 681 AN: 4820

European-Finnish (FIN) AF: 0.220 AC: 2331 AN: 10602

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

European-Non Finnish (NFE) AF: 0.148 AC: 10089 AN: 68004

Other (OTH) AF: 0.123 AC: 260 AN: 2110

Alfa AF: 0.122 Hom.: 1034

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
PhyloP100		-0.062
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: rs13218331; hg19: chr6-32411362; COSMIC: COSV107495290;