chr6-32442360-T-G

Variant names:

• chr6-32442360-T-G
• rs3129883
• NM_019111.5:c.83-88T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019111.5(HLA-DRA):​c.83-88T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000523 in 1,337,446 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 32 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019111.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	NM_019111.5	MANE Select	c.83-88T>G		intron	N/A	NP_061984.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	ENST00000395388.7	TSL:6 MANE Select	c.83-88T>G		intron	N/A	ENSP00000378786.2
	HLA-DRA	ENST00000374982.5	TSL:6	c.83-88T>G		intron	N/A	ENSP00000364121.5
	ENSG00000299747	ENST00000766007.1		n.163-4100A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000523 AC: 7 AN: 1337446 Hom.: 0 AF XY: 0.00000899 AC XY: 6 AN XY: 667096

African (AFR) AF: 0.00 AC: 0 AN: 31114

American (AMR) AF: 0.00 AC: 0 AN: 42546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23280

East Asian (EAS) AF: 0.00 AC: 0 AN: 39056

South Asian (SAS) AF: 0.00 AC: 0 AN: 77324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 0.00000691 AC: 7 AN: 1012298

Other (OTH) AF: 0.00 AC: 0 AN: 56250

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 42947

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		-0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3129883; hg19: chr6-32410137;