ENST00000422863.1:c.-39+2012C>T

Variant names:

• chr6-32634921-C-T
• rs2040410
• ENST00000422863.1:c.-39+2012C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422863.1(HLA-DQA1):​c.-39+2012C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,232 control chromosomes in the GnomAD database, including 933 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 0.10 (933 hom., cov: 33)
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 26 publications found

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 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. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1-AS1	XR_007059544.1	n.*70G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000422863.1	c.-39+2012C>T		intron_variant	Intron 3 of 3	6		ENSP00000405797.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15539 AN: 152116 Hom.: 935 Cov.: 33

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.0631

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0966

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15535 AN: 152232 Hom.: 933 Cov.: 33 AF XY: 0.100 AC XY: 7478 AN XY: 74446

African (AFR) AF: 0.0711 AC: 2954 AN: 41534

American (AMR) AF: 0.108 AC: 1653 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3468

East Asian (EAS) AF: 0.0626 AC: 325 AN: 5190

South Asian (SAS) AF: 0.121 AC: 583 AN: 4824

European-Finnish (FIN) AF: 0.0908 AC: 962 AN: 10596

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.126 AC: 8535 AN: 68002

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.0583 Hom.: 73

Bravo AF: 0.100

Asia WGS AF: 0.0670 AC: 232 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.58
PhyloP100		-0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2040410; hg19: chr6-32602698;